SPINE20 Recommendations 2024 -Spinal Disability: Social Inclusion as a Key to Prevention and Management.

Spine disorders are the leading cause of disability worldwide. To promote social inclusion, it is essential to ensure that people can participate in their societies by improving their ability, opportunities, and dignity, through access to high-quality, evidence-based, and affordable spine services for all.To achieve this goal, SPINE20 recommends six actions.- SPINE20 recommends that G20 countries deliver evidence-based education to the community health workers and primary care clinicians to promote best practice for spine health, especially in underserved communities.- SPINE20 recommends that G20 countries deliver evidence-based, high-quality, cost-effective spine care interventions that are accessible, affordable and beneficial to patients.- SPINE20 recommends that G20 countries invest in Health Policy and System Research (HPSR) to generate evidence to develop and implement policies aimed at integrating rehabilitation in primary care to improve spine health.- SPINE20 recommends that G20 countries support ongoing research initiatives on digital technologies including artificial intelligence, regulate digital technologies, and promote evidence-based, ethical digital solutions in all aspects of spine care, to enrich patient care with high value and quality.- SPINE20 recommends that G20 countries prioritize social inclusion by promoting equitable access to comprehensive spine care through collaborations with healthcare providers, policymakers, and community organizations.- SPINE20 recommends that G20 countries prioritize spine health to improve the well-being and productivity of their populations. Government health systems are expected to create a healthier, more productive, and equitable society for all through collaborative efforts and sustained investment in evidence-based care and promotion of spine health.

Utility of combining frailty and comorbid disease indices in predicting outcomes following craniotomy for adult primary brain tumors: A mixed-effects model analysis using the nationwide readmissions database.

OBJECTIVE: The escalating healthcare expenditures in the United States, particularly in neurosurgery, necessitate effective tools for predicting patient outcomes and optimizing resource allocation. This study explores the utility of combining frailty and comorbidity indices, specifically the Johns Hopkins Adjusted Clinical Groups (JHACG) frailty index and the Elixhauser Comorbidity Index (ECI), in predicting hospital length of stay (LOS), non-routine discharge, and one-year readmission in patients undergoing craniotomy for benign and malignant primary brain tumors. METHODS: Leveraging the Nationwide Readmissions Database (NRD) for 2016-2019, we analyzed data from 645 patients with benign and 30,991 with malignant tumors. Frailty, ECI, and frailty + ECI were assessed as predictors using generalized linear mixed-effects models. Receiver operating characteristic (ROC) curves evaluated predictive performance. RESULTS: Patients in the benign tumor cohort had a mean LOS of 8.1 ± 15.1 days, and frailty + ECI outperformed frailty alone in predicting non-routine discharge (AUC 0.829 vs. 0.820, p = 0.035). The malignant tumor cohort patients had a mean LOS of 7.9 ± 9.1 days. In this cohort, frailty + ECI (AUC 0.821) outperformed both frailty (AUC 0.744, p < 0.0001) and ECI alone (AUC 0.809, p < 0.0001) in predicting hospital LOS. Frailty + ECI (AUC 0.831) also proved superior to frailty (AUC 0.809, p < 0.0001) and ECI alone (AUC 0.827, p < 0.0001) in predicting non-routine discharge location for patients with malignant tumors. All indices performed comparably to one another as a predictor of readmission in both cohorts. CONCLUSION: This study highlights the synergistic predictive capacity of frailty + ECI, especially in malignant tumor cases, and further suggests that comorbid diseases may greatly influence perioperative outcomes more than frailty. Enhanced risk assessment could aid clinical decision-making, patient counseling, and resource allocation, ultimately optimizing patient outcomes.

Empagliflozin-Associated Euglycemic Diabetic Ketoacidosis Masked by Urinary Tract Infection.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated efficacy in slowing the progression of chronic kidney disease (CKD), managing conditions such as congestive heart failure (CHF), and reducing cardiovascular and overall mortality in patients with type 2 diabetes mellitus (T2DM). However, their use is associated with complications, including euglycemic diabetic ketoacidosis (euDKA), genital fungal infections, and urinary tract infections (UTIs). Although rare, complications like euDKA can lead to serious consequences if not promptly addressed, as illustrated by this case report of a 90-year-old man with ischemic cardiomyopathy and type 2 diabetes who developed both euDKA and a UTI while on SGLT2 inhibitor therapy. Early identification of euDKA from SGLT2 inhibitor usage prompted cessation of the SGLT2 inhibitor and administration of insulin infusion, ultimately resolving the life-threatening condition.

Contemporary intergeneric hybridization and backcrossing among birds-of-paradise.

Despite large differences in morphology, behavior and lek-mating strategies the birds-of-paradise are known to hybridize occasionally, even across different genera. Many of these bird-of-paradise hybrids were originally described as distinct species based on large morphological differences when compared to recognized species. Nowadays, these specimens are generally recognized as hybrids based on morphological assessments. Having fascinated naturalists for centuries, hybrid specimens of birds-of-paradise have been collected and the specimens kept in Natural History Collections. In the present study, we utilize this remarkable resource in a museomics framework and evaluate the genomic composition of most described intergeneric hybrids and some intrageneric hybrids. We show that the majority of investigated specimens are first-generation hybrids and that the parental species, in most cases, are in line with prior morphological assessments. We also identify two specimens that are the result of introgressive hybridization between different genera. Additionally, two specimens exhibit hybrid morphologies but have no identifiable signals of hybridization, which may indicate that minor levels of introgression can have large morphological effects. Our findings provide direct evidence of contemporary introgressive hybridization taking place between genera of birds-of-paradise in nature, despite markedly different morphologies and lek-mating behaviors.

The Effectiveness of the Surgical Correction of Vesicoureteral Reflux on Febrile Urinary Tract Infections after a Kidney Transplant: A Single-Center Retrospective Study.

Background/Objectives: Vesicoureteral reflux (VUR) is considered one of the major causes of post-renal transplant febrile urinary tract infections (UTI), leading to impaired renal function and the premature loss of the renal graft. We aimed to evaluate whether surgical VUR correction, such as open redo ureteric reimplantation, could be an option for treatment and provide better outcomes in post-transplant care for patients with UTI compared to their pre-VUR correction clinical state. Methods: Our study presents a retrospective analysis of 10 kidney transplant recipients with febrile UTI at the Renal Transplant Service of a Brazilian public hospital from 2010 to 2020. We selected patients who primarily underwent a surgical correction of post-transplant VUR, which was corrected by extravesical reimplantation without a stent in all patients by the same professional surgeon. Results: From 710 patients who received kidney transplants, 10 patients (1.4%) suffered from febrile UTI post-transplant and underwent surgical correction for VUR. Despite the study's limitations, such as its retrospective nature and limited sample size, the efficacy of open extravesical ureteral reimplantation in reducing post-operative febrile UTI in renal transplant patients was observed. Conclusions: As febrile UTI can contribute significantly to patient mortality after kidney transplantation and VUR emerges as a major cause of post-transplant febrile UTI, it is essential to treat it and consider the surgical outcome. This study emphasizes the timely detection and effective treatment of VUR via extravesical techniques to reduce febrile UTI occurrences post-transplant and it contributes insights into the role of surgical interventions in addressing VUR-related complications post-kidney transplantation.

Pituitary Apoplexy: a re-appraisal of risk factors and best management strategies in the COVID-19 era.

Pituitary apoplexy (PA) is a clinical syndrome caused by acute hemorrhage and/or infarction of the pituitary gland, most commonly in the setting of a pituitary macroadenoma. PA generally presents with severe headache, nausea, vomiting, visual disturbance, and, in more severe cases, altered mental status. Many factors have been attributed to the risk of developing PA, including most recently, numerous reports showcasing an association with COVID-19 infection or vaccination. Initial management of PA includes evaluation and correction of deficient hormones and electrolytes and an assessment if surgical decompression to relieve pressure on optic nerves and other brain structures is needed. While prompt recognition and treatment are crucial to avoid morbidity and mortality, in the modern era, PA is less commonly considered a true neurosurgical emergency requiring immediate (< 24 h) surgical decompression. Traditionally, surgical decompression has been the standard of care for significant mass effects. However, several studies have shown similar outcomes in visual and hormonal recovery with either surgical decompression or conservative medical management. Unfortunately, most evidence on optimal management strategies is limited to retrospective case series, small prospective studies, and one multi-center observational study. This review aims to provide the most up-to-date evidence on the role of COVID-19 in PA and best management strategies.

Endothelial Cells Increase Mesenchymal Stem Cell Differentiation in Scaffold-Free 3D Vascular Tissue.

In this study, we present a versatile, scaffold-free approach to create ring-shaped engineered vascular tissue segments using human mesenchymal stem cell-derived smooth muscle cells (hMSC-SMCs) and endothelial cells (ECs). We hypothesized that incorporation of ECs would increase hMSC-SMC differentiation without compromising tissue ring strength or fusion to form tissue tubes. Undifferentiated hMSCs and ECs were co-seeded into custom ring-shaped agarose wells using four different concentrations of ECs: 0%, 10%, 20%, and 30%. Co-seeded EC and hMSC rings were cultured in SMC differentiation medium for a total of 22 days. Tissue rings were then harvested for histology, Western blotting, wire myography, and uniaxial tensile testing to examine their structural and functional properties. Differentiated hMSC tissue rings comprising 20% and 30% ECs exhibited significantly greater SMC contractile protein expression, endothelin-1 (ET-1)-meditated contraction, and force at failure compared with the 0% EC rings. On average, the 0%, 10%, 20%, and 30% EC rings exhibited a contractile force of 0.745 ± 0.117, 0.830 ± 0.358, 1.31 ± 0.353, and 1.67 ± 0.351 mN (mean ± standard deviation [SD]) in response to ET-1, respectively. Additionally, the mean maximum force at failure for the 0%, 10%, 20%, and 30% EC rings was 88.5 ± 36. , 121 ± 59.1, 147 ± 43.1, and 206 ± 0.8 mN (mean ± SD), respectively. Based on these results, 30% EC rings were fused together to form tissue-engineered blood vessels (TEBVs) and compared with 0% EC TEBV controls. The addition of 30% ECs in TEBVs did not affect ring fusion but did result in significantly greater SMC protein expression (calponin and smoothelin). In summary, co-seeding hMSCs with ECs to form tissue rings resulted in greater contraction, strength, and hMSC-SMC differentiation compared with hMSCs alone and indicates a method to create a functional 3D human vascular cell coculture model.

Vascular tissues bioprinted with smooth muscle cell-only bioinks in support baths mimic features of native coronary arteries.

This study explores the bioprinting of a smooth muscle cell-only bioink into ionically crosslinked oxidized methacrylated alginate (OMA) microgel baths to create self-supporting vascular tissues. The impact of OMA microgel support bath methacrylation degree and cell-only bioink dispensing parameters on tissue formation, remodeling, structure and strength was investigated. We hypothesized that reducing dispensing tip diameter from 27 G (210µm) to 30 G (159µm) for cell-only bioink dispensing would reduce tissue wall thickness and improve the consistency of tissue dimensions while maintaining cell viability. Printing with 30 G tips resulted in decreased mean wall thickness (318.6µm) without compromising mean cell viability (94.8%). Histological analysis of cell-only smooth muscle tissues cultured for 14 d in OMA support baths exhibited decreased wall thickness using 30 G dispensing tips, which correlated with increased collagen deposition and alignment. In addition, a TUNEL assay indicated a decrease in cell death in tissues printed with thinner (30 G) dispensing tips. Mechanical testing demonstrated that tissues printed with a 30 G dispensing tip exhibit an increase in ultimate tensile strength compared to those printed with a 27 G dispensing tip. Overall, these findings highlight the importance of precise control over bioprinting parameters to generate mechanically robust tissues when using cell-only bioinks dispensed and cultured within hydrogel support baths. The ability to control print dimensions using cell-only bioinks may enable bioprinting of more complex soft tissue geometries to generatein vitrotissue models.

Exploring the use of exhaled breath as a diagnostic tool for pulmonary TB.

Despite its historical decline, TB remains a significant cause of infectious disease-related global deaths. The lack of reliable diagnostic tests for vulnerable groups, such as children and immunocompromised patients, remains a challenge for TB control. For decades, it has been recognised that exhaled breath has great potential as a non-invasive and universally accessible clinical alternative to sputum and invasive sampling methods. Although translation into clinical practice has not yet occurred, there has been significant progress with promising results in various applications, including diagnosis, estimation of infectiousness, and monitoring of treatment response. More recently, the COVID-19 pandemic reignited global interest in this field and technological advances have further accelerated its development. In the coming decade, breath sampling will enhance our understanding of respiratory infectious diseases and host-immune responses, which may lead to clinical applications. Here we discuss the diagnostic landscape of TB and the current state of the art of breath sampling.

Rebalancing the motor circuit restores movement in a Caenorhabditis elegans model for TDP-43 toxicity.

Amyotrophic lateral sclerosis can be caused by abnormal accumulation of TAR DNA-binding protein 43 (TDP-43) in the cytoplasm of neurons. Here, we use a C. elegans model for TDP-43-induced toxicity to identify the biological mechanisms that lead to disease-related phenotypes. By applying deep behavioral phenotyping and subsequent dissection of the neuromuscular circuit, we show that TDP-43 worms have profound defects in GABA neurons. Moreover, acetylcholine neurons appear functionally silenced. Enhancing functional output of repressed acetylcholine neurons at the level of, among others, G-protein-coupled receptors restores neurotransmission, but inefficiently rescues locomotion. Rebalancing the excitatory-to-inhibitory ratio in the neuromuscular system by simultaneous stimulation of the affected GABA- and acetylcholine neurons, however, not only synergizes the effects of boosting individual neurotransmitter systems, but instantaneously improves movement. Our results suggest that interventions accounting for the altered connectome may be more efficient in restoring motor function than those solely focusing on diseased neuron populations.

The dehydration mechanism of Na and K birnessites: a comprehensive multitechnique study.

The structural, spectroscopic and electronic properties of Na and K birnessites were investigated from ambient conditions (birA) to complete dehydration, and the involved mechanisms were scrutinized. Density Functional Theory (DFT) simulations were employed to derive structural models for lamellar A0.33MnO2·xH2O (A = Na+ or K+, x = 0 or 0.66), subsequently compared with the experimental results obtained for Na0.30MnO2·0.75H2O and K0.22MnO2·0.77H2O materials. Thermal analysis (TGA-DSC), X-ray diffraction (XRD), Fourier Transform Infrared (FTIR) spectroscopy, and Near Ambient Pressure X-ray Photoemission Spectroscopy (NAP-XPS) measurements were conducted for both birnessites. Dehydration under vacuum, annealing, or controlled relative humidity were considered. Results indicated that complete birnessite dehydration was a two-stage process. In the first stage, water removal from the interlayer of fully hydrated birnessite (birA) down to a molar H2O/A ratio of ∼2 (birB) led to the progressive shrinkage of the interlayer distance (3% for Na birnessite, 1% for K birnessite). In the second stage, water-free (birC) domains with a shorter interlayer distance (20% for Na birnessite, 10% for K birnessite) appeared and coexisted with birB domains. Then, birB was essentially transformed into birC when complete dehydration was achieved. The vibrational properties of birA were consistent with strong intermolecular interactions among water molecules, whereas partially dehydrated birnessite (birB) showed a distinct feature, with 3 (for Na-bir) and 2 (for K-bir) vibrations that were reproduced by DFT calculations for organized water into the interlayer (x = 0.66). The study also demonstrated that the electronic structure of Na birnessite depends on the interlayer water content. The external Na+ electronic level (Na 2p) was slightly destabilized (+0.3 eV binding energy) under near ambient conditions (birA) compared to drier conditions (birB and birC).

Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer.

Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.

Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.

BACKGROUND: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk. METHODS: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated. RESULTS: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 × 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 × 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk. CONCLUSIONS: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

XFEM for Composites, Biological, and Bioinspired Materials: A Review.

The eXtended finite element method (XFEM) is a powerful tool for structural mechanics, assisting engineers and designers in understanding how a material architecture responds to stresses and consequently assisting the creation of mechanically improved structures. The XFEM method has unraveled the extraordinary relationships between material topology and fracture behavior in biological and engineered materials, enhancing peculiar fracture toughening mechanisms, such as crack deflection and arrest. Despite its extensive use, a detailed revision of case studies involving XFEM with a focus on the applications rather than the method of numerical modeling is in great need. In this review, XFEM is introduced and briefly compared to other computational fracture models such as the contour integral method, virtual crack closing technique, cohesive zone model, and phase-field model, highlighting the pros and cons of the methods (e.g., numerical convergence, commercial software implementation, pre-set of crack parameters, and calculation speed). The use of XFEM in material design is demonstrated and discussed, focusing on presenting the current research on composites and biological and bioinspired materials, but also briefly introducing its application to other fields. This review concludes with a discussion of the XFEM drawbacks and provides an overview of the future perspectives of this method in applied material science research, such as the merging of XFEM and artificial intelligence techniques.

The Discrepancy Between Hemoglobin A1c and Glucose Management Indicators in 26 Patients Treated With Continuous Glucose Monitoring in an Internal Medicine Residency Clinic.

We conducted a retrospective observational cohort study between 2020 and 2023 in 26 patients with type 1 and type 2 diabetes mellitus (DM) who were using 3-4 injections per day of insulin and were monitored by continuous glucose monitoring (CGM). The goal of this retrospective observational cohort study is to compare these two metrics in an internal medicine community primary care residency clinic. We used CGM devices, Dexcom G6 and G7, and Freestyle Libre 3. The goal was to compare the patient's hemoglobin A1c (HbA1c) taken during their clinic visit by phlebotomy as a marker for diabetic control with an estimated HbA1c glucose management indicator (GMI) derived from the 30-day CGM readings. HbA1c is derived from the blood, while the GMI value is derived from the interstitial fluid. Both parameters were taken within 30 days of each other. GMI was taken in the last 30 days. We excluded patients with known anemia, chronic kidney disease, polycythemia, cirrhosis of the liver, or metabolic dysfunction associated with steatohepatitis (MASH) because disease states can affect the measured HbA1c. Also, pregnant and African American patients were excluded. We concluded the measured HbA1c was 0.34% (4 mmol/mol) higher than the CGM-derived GMI. The relationship between factors that affect glycemic control was discussed in the article, as well as the future utilization of them in improving diabetic control and management. As the use of CGM continues to grow, addressing differences between laboratory-measured HbA1c and CGM-derived GMI is critical.

Reprogramming the pancreatic cancer stroma and immune landscape by a silicasome nanocarrier delivering nintedanib, a protein tyrosine kinase inhibitor.

The prevailing desmoplastic stroma and immunosuppressive microenvironment within pancreatic ductal adenocarcinoma (PDAC) pose substantial challenges to therapeutic intervention. Despite the potential of protein tyrosine kinase (PTK) inhibitors in mitigating the desmoplastic stromal response and enhancing the immune milieu, their efficacy is curtailed by suboptimal pharmacokinetics (PK) and insufficient tumor penetration. To surmount these hurdles, we have pioneered a novel strategy, employing lipid bilayer-coated mesoporous silica nanoparticles (termed "silicasomes") as a carrier for the delivery of Nintedanib. Nintedanib, a triple PTK inhibitor that targets vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor receptors, was encapsulated in the pores of silicasomes via a remote loading mechanism for weak bases. This innovative approach not only enhanced pharmacokinetics and intratumor drug concentrations but also orchestrated a transformative shift in the desmoplastic and immune landscape in a robust orthotopic KRAS-mediated pancreatic carcinoma (KPC) model. Our results demonstrate attenuation of vascular density and collagen content through encapsulated Nintedanib treatment, concomitant with significant augmentation of the CD8+/FoxP3+ T-cell ratio. This remodeling was notably correlated with tumor regression in the KPC model. Strikingly, the synergy between encapsulated Nintedanib and anti-PD-1 immunotherapy further potentiated the antitumor effect. Both free and encapsulated Nintedanib induced a transcriptional upregulation of PD-L1 via the extracellular signal-regulated kinase (ERK) pathway. In summary, our pioneering approach involving the silicasome carrier not only improved antitumor angiogenesis but also profoundly reshaped the desmoplastic stromal and immune landscape within PDAC. These insights hold excellent promise for the development of innovative combinatorial strategies in PDAC therapy.

RTN2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.

Heterozygous RTN2 variants have been previously identified in a limited cohort of families affected by autosomal dominant spastic paraplegia (SPG12-OMIM:604805) with a variable age of onset. Nevertheless, the definitive validity of SPG12 remains to be confidently confirmed due to the scarcity of supporting evidence. In this study, we identified and validated seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) using exome, genome and Sanger sequencing coupled with deep-phenotyping. All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity and hyperreflexia, with onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Despite a slowly progressive disease course, all patients remained ambulatory over a mean disease duration of 19.71 ± 13.70 years. Characterization of Caenorhabditis elegans RTN2 homologous loss-of-function variants demonstrated morphological and behavioural differences compared with the parental strain. Treatment of the mutant with an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences, suggesting a potential therapeutic benefit for RTN2-disorder. Despite RTN2 being an endoplasmic reticulum (ER)-resident membrane shaping protein, our analysis of patient fibroblast cells did not find significant alterations in ER structure or the response to ER stress. Our findings delineate a distinct form of autosomal recessive dHMN with pyramidal features associated with RTN2 deficiency. This phenotype shares similarities with SIGMAR1-related dHMN and Silver-like syndromes, providing valuable insights into the clinical spectrum and potential therapeutic strategies for RTN2-related dHMN.

Spontaneous sphenoid sinus meningocele with associated amenorrhea and headache: illustrative case.

BACKGROUND: Developmental meningoceles of the sphenoid sinus are uncommon. When encountered, they are often associated with cerebrospinal fluid (CSF) rhinorrhea. OBSERVATIONS: The authors present the case of a 27-year-old female with a large meningocele eroding through the sella turcica and sphenoid sinus into the nasopharynx. The patient presented with intractable headaches and amenorrhea without CSF rhinorrhea. LESSONS: The patient underwent an endoscopic endonasal transsphenoidal reduction of the meningocele with reelevation of the pituitary gland and skull base reconstruction with abdominal fat graft and nasoseptal flap.

Implications of headwater contact zones for the riverine barrier hypothesis: a case study of the Blue-capped Manakin (Lepidothrix coronata).

Rivers frequently delimit the geographic ranges of species in the Amazon Basin. These rivers also define the boundaries between genetic clusters within many species, yet river boundaries have been documented to break down in headwater regions where rivers are narrower. To explore the evolutionary implications of headwater contact zones in Amazonia, we examined genetic variation in the Blue-capped Manakin (Lepidothrix coronata), a species previously shown to contain several genetically and phenotypically distinct populations across the western Amazon Basin. We collected restriction site-associated DNA sequence data (RADcap) for 706 individuals and found that spatial patterns of genetic structure indicate several rivers, particularly the Amazon and Ucayali, are dispersal barriers for L. coronata. We also found evidence that genetic connectivity is elevated across several headwater regions, highlighting the importance of headwater gene flow for models of Amazonian diversification. The headwater region of the Ucayali River provided a notable exception to findings of headwater gene flow by harboring non-admixed populations of L. coronata on opposite sides of a < 1-km-wide river channel with a known dynamic history, suggesting that additional prezygotic barriers may be limiting gene flow in this region.