Exploring drivers of environmental degradation in urban centres of developing countries: a case study.

A serene and pollution-free environment is the desire of the United Nations through its Sustainable Development Goal 11. This research was designed to explore various human endeavours that drive pollution in urban environs in the developing countries with Iwo, Nigeria, as a case study. Out of the four hundred and fifty (450) respondents that were randomly selected, 410 copies of structured questionnaire were completed and returned for analysis. Descriptive and inferential analytical methods were adopted for the purpose data analysis. Of all the respondents, 69.5% were females, and 95.1% were between the ages of 18 and 65 years, while 85.3% of the respondents have a minimum of secondary education. The dataset was further subjected to KMO and Bartlett's Test, the results which showed that the data is factorable with 68% at confidence level of p ≤ 0.05. Factor analysis extracted 7 variables out of the 21 variables analysed. The identified and extracted variables explained 87.745% of the variance explained by the extracted factors and their respective explanation variance are as follows: (i) palm oil activities in urban centres (20.521%); (ii) food vending outlets (14.153%); (iii) individual households within cities (13.786%); (iv) activities in the slaughter slabs and houses (11.384%); (v) auto repair workshops (9.812%); (vi) unplanned refuse dumpsites (9.571%); and (vii) in-urban free-range keeping of animals (8.745%). This research should give further insights to stakeholders, especially the policy makers in urban planning on subduing the challenges of unabated urban degradation in developing nations if human comfort and sustainability will be enhanced and that SDG 11 will be a reality come 2030.

Growth modulation response in vertebral body tethering depends primarily on magnitude of concave vertebral body growth.

PURPOSE: There is variability in clinical outcomes with vertebral body tethering (VBT) partly due to a limited understanding of the growth modulation (GM) response. We used the largest sample of patients with 3D spine reconstructions to characterize the vertebra and disc morphologic changes that accompany growth modulation during the first two years following VBT. METHODS: A multicenter registry was used to identify idiopathic scoliosis patients who underwent VBT with 2 years of follow-up. Calibrated biplanar X-rays obtained at longitudinal timepoints underwent 3D reconstruction to obtain precision morphological measurements. GM was defined as change in instrumented coronal angulation from post-op to 2-years. RESULTS: Fifty patients (mean age: 12.5 ± 1.3yrs) were analyzed over a mean of 27.7 months. GM was positively correlated with concave vertebra height growth (r = 0.57, p < 0.001), 3D spine length growth (r = 0.36, p = 0.008), and decreased convex disc height (r = - 0.42, p = 0.002). High modulators (patients experiencing GM > 10°) experienced an additional 1.6 mm (229% increase) of mean concave vertebra growth during study period compared to the Poor Modulators (GM < - 10°) group, (2.3 vs. 0.7 mm, p = 0.039), while convex vertebra height growth was similar (1.3 vs. 1.4 mm, p = 0.91). CONCLUSION: When successful, VBT enables asymmetric vertebra body growth, leading to continued postoperative coronal angulation correction (GM). A strong GM response is correlated with concave vertebral body height growth and overall instrumented spine growth. A poor GM response is associated with an increase in convex disc height (suspected tether rupture). Future studies will investigate the patient and technique-specific factors that influence increased growth remodeling.

Evolutionary insights into sequence modifications governing chitin recognition and chitinase inactivity in YKL-40 (HC-gp39, CHI3L1).

YKL-40, also known as human cartilage glycoprotein-39 (HC-gp39) or CHI3L1, shares structural similarities with chitotriosidase (CHIT1), an active chitinase, but lacks chitinase activity. Despite being a biomarker for inflammatory disorders and cancer, the reasons for YKL-40's inert chitinase function have remained elusive. This study reveals that the loss of chitinase activity in YKL-40 has risen from multiple sequence modifications influencing its chitin affinity. Contrary to the common belief associating the lack of chitinase activity with amino acid substitutions in the catalytic motif, attempts to activate YKL-40 by creating two amino acid mutations in the catalytic motif (MT-YKL-40) proved ineffective. Subsequent exploration that included creating chimeras of MT-YKL-40 and CHIT1 catalytic domains (CatDs) identified key exons responsible for YKL-40 inactivation. Introducing YKL-40 exons 3, 6, or 8 into CHIT1 CatD resulted in chitinase inactivation. Conversely, incorporating CHIT1 exons 3, 6, and 8 into MT-YKL-40 led to its activation. Our recombinant proteins exhibited properly formed disulfide bonds, affirming a defined structure in active molecules. Biochemical and evolutionary analysis indicated that the reduced chitinase activity of MT-YKL-40 correlates with specific amino acids in exon 3. M61I and T69W substitutions in CHIT1 CatD diminished chitinase activity and increased chitin binding. Conversely, substituting I61 with M and W69 with T in MT-YKL-40 triggered chitinase activity while reducing the chitin-binding activity. Thus, W69 plays a crucial role in a unique subsite within YKL-40. These findings emphasize that YKL-40, though retaining the structural framework of a mammalian chitinase, has evolved to recognize chitin while surrendering chitinase activity.

The genome sequence of the Water Veneer, Acentria ephemerella (Denis & Schiffermüller, 1775).

We present a genome assembly from an individual male Acentria ephemerella (the Water Veneer; Arthropoda; Insecta; Lepidoptera; Crambidae). The genome sequence is 340.8 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.35 kilobases in length. Gene annotation of this assembly on Ensembl identified 17,748 protein coding genes.

End of life care at home: The role of critical care transfer services.

Background: Most people would rather die at home than in hospital but only 18% of patients do so. Palliative care focuses on the physical, spiritual and psychosocial wellbeing of patients and their families, which should include facilitating transfers home when possible. Patients can have more autonomy over their care and be surrounded by loved ones which can have a significant impact on their quality of life. In this article we describe two cases of home repatriation for palliation. Case 1 describes the transfer of a patient with difficulties and gaps in planning, but with a safe transfer ultimately. Case 2 recounts a more comprehensive planning process emphasising collaboration between teams. Benefits and difficulties of palliative critical care transfers: Facilitating home-based care aligns with patients' desires for familiar surroundings and emotional support. A secondary benefit is that releasing a bed space allows another patient to receive critical care treatment. Challenges of palliative critical care transfers include needing a highly trained team and thorough planning. Early discussion with the family and community palliative care teams makes this a more feasible option for patients. Conclusion: A multidisciplinary team of hospital and community healthcare professionals working with the patient and their family can facilitate the transfer from intensive care to allow them to die at a place of their choosing. We should aim to fulfil these wishes at the end of life as it can greatly improve the patient's and their family's physical and emotional wellbeing during this difficult time.

Danicamtiv affected isometric force and cross-bridge kinetics similarly in skinned myocardial strips from male and female rats.

Myotropes are pharmaceuticals that have recently been developed or are under investigation for the treatment of heart diseases. Myotropes have had varied success in clinical trials. Initial research into myotropes have widely focused on animal models of cardiac dysfunction in comparison with normal animal cardiac physiology-primarily using males. In this study we examined the effect of danicamtiv, which is one type of myotrope within the class of myosin activators, on contractile function in permeabilized (skinned) myocardial strips from male and female Sprague-Dawley rats. We found that danicamtiv increased steady-state isometric force production at sub-maximal calcium levels, leading to greater Ca2+-sensitivity of contraction for both sexes. Danicamtiv did not affect maximal Ca2+-activated force for either sex. Sinusoidal length-perturbation analysis was used to assess viscoelastic myocardial stiffness and cross-bridge cycling kinetics. Data from these measurements did not vary with sex, and the data suggest that danicamtiv slows cross-bridge cycling kinetics. These findings imply that danicamtiv increases force production via increasing cross-bridge contributions to activation of contraction, especially at sub-maximal Ca2+-activation. The inclusion of both sexes in animal models during the formative stages of drug development could be helpful for understanding the efficacy or limitation of a drug's therapeutic impact on cardiac function.

Early warning signals of the termination of the African Humid Period(s).

The transition from a humid green Sahara to today's hyperarid conditions in northern Africa ~5.5 thousand years ago shows the dramatic environmental change to which human societies were exposed and had to adapt to. In this work, we show that in the 620,000-year environmental record from the Chew Bahir basin in the southern Ethiopian Rift, with its decadal resolution, this one thousand year long transition is particularly well documented, along with 20-80 year long droughts, recurring every ~160 years, as possible early warnings. Together with events of extreme wetness at the end of the transition, these droughts form a pronounced climate "flickering", which can be simulated in climate models and is also present in earlier climate transitions in the Chew Bahir environmental record, indicating that transitions with flickering are characteristic of this region.

Clinicopathologic characteristics and treatment outcomes of pancreatic cancer patients at a tertiary referral hospital in Kenya.

The global incidence of pancreatic cancer (PC) continues to steadily increase whereas its prognosis remains poor. Previous studies have suggested worse outcomes among individuals of African descent. The characteristics of patients with PC in Kenya, and their contemporary management and survival outcomes remain largely unknown. This study aimed to describe the clinical and pathologic characteristics, management, and outcomes of patients diagnosed with PC at Kenyatta National Hospital (KNH), a tertiary referral hospital in Kenya. Records of 242 patients diagnosed with PC at KNH between 1st January 2014 and 30th September 2021 were assessed in this retrospective cohort study. Data on their clinical, histopathologic, and treatment characteristics was presented as mean (± standard deviation) and/or median (interquartile range) for continuous variables and frequency (percentage) for categorical variables. Kaplan-Meier and Cox proportional hazard ratios were used for survival analysis. PC occurred in a young population, the median age being 58.5 years (inter-quartile range 35-88). The majority of tumours (54%) were metastatic at diagnosis, while 28% and 14% were stage III and stage I/II, respectively. Surgical resections with curative intent were performed on 7% overall and 44% of stage I/II cases. The majority of patients with stage I/II disease (52.9%) received chemotherapy whereas the majority with stage III and IV disease received the best supportive care only (62.7% and 64.9%, respectively). Patients who underwent surgical resection (HR for mortality 0.20, 95% CI 0.05-0.83, p = 0.021) and chemotherapy (HR for mortality 0.15, 95% CI 0.08-0.29, p < 0.001) had significantly improved survival, reflecting a more favourable stage of the disease more amenable to aggressive therapies. The median survival time was 3 months and the 1-year survival rate was 32%.

Three-dimensional vertebral shape changes confirm growth modulation after anterior vertebral body tethering for idiopathic scoliosis.

PURPOSE: To evaluate three-dimensional (3D) vertebra and disk shape changes over 2 years following anterior vertebral body tether (AVBT) placement in patients with idiopathic scoliosis (IS). METHODS: Patients with right thoracic IS treated with AVBT were retrospectively evaluated. 3D reconstructions were created from biplanar radiographs. Vertebral body and disk height (anterior, posterior, left and right) and shape (wedging angle) were recorded over the three apical segments in the local vertebral reference planes. Changes in height and wedging were measured through 2 years postoperatively. Change in patient height was correlated with changes in the spine dimensions. RESULTS: Forty-nine patients (Risser 0-3, Sanders 2-4) were included. The mean age was 12.2 ± 1.4 years (range 8-14). The mean coronal curve was 51 ± 10° preoperatively, 31 ± 9° at first postoperative time point and 27 ± 11° at 2-year follow-up (p < 0.001). The mean patient height increased 8 cm by 2 years (p < 0.001). The left side of the spine (vertebra + disc) grew in height by 2.2 mm/level versus 0.7 mm/level on the right side (p < 0.001). This differential growth was composed of 0.5 mm/vertebral level and 1.0 mm/disk level. Evaluation of the change in disk heights showed significantly decreased height anteriorly (- 0.4 mm), posteriorly (- 0.3 mm) and on the right (- 0.5 mm) from FE to 2 years. Coronal wedging reduced 2.3°/level with 1.1°/vertebral level change and 1.2°/disk level. There was no differential growth in the sagittal plane (anterior/posterior height). Patient height change moderately correlated with 3D measures of vertebra + disk shape changes. CONCLUSIONS: Three-dimensional analysis confirms AVBT in skeletally immature patients results in asymmetric growth of the apical spine segments. The left (untethered) side length increased more than 3 × than the right (tethered) side length with differential effects observed within the vertebral bodies and disks, each correlating with overall patient height change.

Disparities in Indications and Outcomes Reporting for Spinal Column Shortening for Tethered Cord Syndrome: The Need for a Standardized Approach.

STUDY DESIGN: Systematic review. OBJECTIVE: To identify commonly reported indications and outcomes in spinal column shortening (SCS) procedures. SUMMARY OF BACKGROUND DATA: SCS is a surgical procedure used in patients with tethered cord syndrome (TCS)-characterized by abnormal attachment of neural components to surrounding tissues-to shorten the vertebral column, release tension on the spinal cord/neural elements, and alleviate associated symptoms. METHODS: PubMed and EMBASE searches captured SCS literature published between 1950 and 2023. Prospective/retrospective cohort studies and case series were included without age limit or required follow-up period. Review articles without new patient presentations, meta-analyses, systematic reviews, conference abstracts, and letters were excluded. Studies included adult and pediatric patients. RESULTS: The 29 identified studies represented 278 patients (age 5-76 y). In 24.1% of studies, patients underwent primary TCS intervention via SCS. In 41.4% of studies, patients underwent SCS after failed previous primary detethering (24.1% of studies were mixed and 10.3% were unspecified). The most commonly reported non-genitourinary/bowel surgical indications were back pain (55.2%), lower-extremity pain (48.3%), lower-extremity weakness (48.3%), lower-extremity numbness (34.5%), and lower-extremity motor dysfunction (34.5%). Genitourinary/bowel symptoms were most often described as nonspecific bladder dysfunction (58.6%), bladder incontinence (34.5%), and bowel dysfunction (31.0%). After SCS, non-genitourinary/bowel outcomes included lower-extremity pain (44.8%), back pain (31.0%), and lower-extremity sensory and motor function (both 31.0%). Bladder dysfunction (79.3%), bowel dysfunction (34.5%), and bladder incontinence (13.8%) were commonly reported genitourinary/bowel outcomes. In total, 40 presenting surgical indication categories and 33 unique outcome measures were reported across studies. Seventeen of the 278 patients (6.1%) experienced a complication. CONCLUSION: The SCS surgical literature displays variability in operative indications and postoperative outcomes. The lack of common reporting mechanisms impedes higher-level analysis. A standardized outcomes measurement tool, encompassing both patient-reported outcome measures and objective metrics, is necessary. LEVEL OF EVIDENCE: Level 4.

Scoliosis Research Society-22r and Ceiling Effects: Limited Capabilities for Precision-Medicine with Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective registry analysis. OBJECTIVE: To examine predictions of individual Scoliosis Research Society-22r (SRS-22r) questions one year after surgery for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: A precision-medicine approach to AIS surgery will inform patients of the likelihood of achieving particular results from surgery, specifically individual responses to the SRS-22r questionnaire. METHODS: A multi-center AIS registry was queried for surgical AIS patients treated between 2002-2020. Preoperative data collected included standard demographic data, deformity descriptive data, and SRS-22r scores. Postoperative 1yr SRS-22r scores were modeled using ordinal logistic regression. . The highest probability was the most likely response. Model performance was examined by c-statistics, where c>.8 was considered excellent. Ceiling effects were measured by the proportion of patients reporting "5" to each question. RESULTS: 3251 patients contributed data to the study; mean age 14.4 (±2.2) yrs, female 2631 (81%), major thoracic coronal curve 53°, mean lumbar 41°. C-statistic values ranged from .6 (poor) to .8 (excellent) evidence of varied predictive capabilities. Q17 ("days off work/school", c = .84, ceiling achieved 75%) and Q15 ("financial difficulties", c = .86, ceiling achieved 82%) had the greatest predictive capabilities while Q11 ("pain medication", c=.73, ceiling achieved 67%), Q10 ("appearance", c=.72, ceiling achieved 35%), and Q19 ("attractive", c=.69, ceiling achieved 37%) performed poorly. CONCLUSION: Prediction of individual SRS-22r item responses perhaps most germane to AIS treatment was poor. Prediction of less relevant outcomes, where ceiling effects are present, was greater as the models chose "5" for all responses. These ceiling effects may limit discrimination and hamper efforts at personalized outcome predictions. LEVEL OF EVIDENCE: 3.

GC Content Across Insect Genomes: Phylogenetic Patterns, Causes and Consequences.

The proportions of A:T and G:C nucleotide pairs are often unequal and can vary greatly between animal species and along chromosomes. The causes and consequences of this variation are incompletely understood. The recent release of high-quality genome sequences from the Darwin Tree of Life and other large-scale genome projects provides an opportunity for GC heterogeneity to be compared across a large number of insect species. Here we analyse GC content along chromosomes, and within protein-coding genes and codons, of 150 insect species from four holometabolous orders: Coleoptera, Diptera, Hymenoptera, and Lepidoptera. We find that protein-coding sequences have higher GC content than the genome average, and that Lepidoptera generally have higher GC content than the other three insect orders examined. GC content is higher in small chromosomes in most Lepidoptera species, but this pattern is less consistent in other orders. GC content also increases towards subtelomeric regions within protein-coding genes in Diptera, Coleoptera and Lepidoptera. Two species of Diptera, Bombylius major and B. discolor, have very atypical genomes with ubiquitous increase in AT content, especially at third codon positions. Despite dramatic AT-biased codon usage, we find no evidence that this has driven divergent protein evolution. We argue that the GC landscape of Lepidoptera, Diptera and Coleoptera genomes is influenced by GC-biased gene conversion, strongest in Lepidoptera, with some outlier taxa affected drastically by counteracting processes.

Intrawound Vancomycin Powder Reduces Delayed Deep Surgical Site Infections Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective. OBJECTIVE: Evaluate whether the use of vancomycin powder (VP) placed in the surgical site prior to wound closure prevents delayed deep surgical site infections (DDI). SUMMARY OF BACKGROUND DATA: DDI after posterior spinal fusion (PSF) in adolescent idiopathic scoliosis (AIS) patients remains a significant major complication. The use of VP to prevent acute surgical site infection has been reported but the impact on DDI is unknown. METHODS: AIS patients treated over the past 20 years with PSF/instrumentation from a large muti-center registry were reviewed. Patients were divided into two groups: intraoperative vancomycin powder placed in the wound (VP) or no antibiotics placed in the wound (NVP). DDI was defined as an infection that occurred >90 days after surgery and required surgical intervention in the operating room. Patients who developed a DDI had secondary verification of VP use or not. Chi square and Kaplan-Meier (K-M) survivorship analyses were used to compare demographics and incident rate of DDI between groups. RESULTS: 4145 cases met inclusion for this study. A total of 43 DDI cases were identified (1.0%). The incidence of DDI for the VP group was 0.2% (4/2111), and 1.9% (39/2034) in the NVP group (P<0.001). Given the difference in follow-up for the 2 groups a Cumulative Survival and Kaplan-Meier analysis revealed the VP group had significantly better "survival" (no DDI) than the NVP group (P<0.001). CONCLUSION: DDIs are significant, adverse events that can greatly complicate patient recovery after PSF for AIS, including rehospitalization. This study found that patients who received VP intraoperatively were 10 times less likely to develop a DDI than those who did not receive VP. Although other advances/changes in surgical techniques may contribute to the significant decrease in infections found in the more recent VP cohort, VP should be considered as a prophylactic measure.

Association of maternal insulin resistance with neonatal insulin resistance and body composition/size: a prospective cohort study in a sub-Saharan African population.

PURPOSE: We prospectively evaluated the association of the insulin resistance of third-trimester Nigerian pregnant women with their newborn infants' insulin resistance and birth size. Pregnancy-associated insulin resistance (IR), often assessed with homeostatic model assessment of IR (HOMA-IR), is associated, especially among women with gestational diabetes (GDM), with abnormal neonatal birth size and body composition, predisposing the baby to metabolic disorders like diabetes and obesity. The associations of maternal IR with neonatal IR, birth size and body composition are less studied in nondiabetic pregnant women, especially in sub-Saharan settings like Nigeria. METHODS: We originally recruited 401 third trimester, nondiabetic pregnant women to a prospective cohort study, followed up until birth. Blood samples of mothers and babies were obtained, respectively, at recruitment and within 24 hours postbirth for fasting serum glucose (FSG) and insulin (FSI) assays, and HOMA-IR was calculated as [(FSI × FSG)/22.5)]. RESULTS: Complete data for 150 mother-baby dyads was analysed: the mothers, with a mean (standard deviation [SD]) age of 31.6 (4.5) years, had live births at a mean (SD) gestational age of 39.2 weeks. The proportions of infants with wasting, stunting, impaired fetal growth (either wasting or stunted), small-for-gestation-age, large-for-gestational-age, low birthweight, and macrosomia were 4.2% (95% confidence interval, 1.1-10.3), 19.7% (12.9-28.0), 23.1% (15.8-31.8), 10.1% (5.3-17.0), 12.6% (7.2-19.9), 0.8% (0.02-4.5), and 5.0% (1.8-10.5), respectively. Maternal HOMA-IR was not associated with neonatal HOMA-IR (p=0.837), birth weight (p=0.416) or body composition measured with weight-length ratio (p=0.524), but birth weight was independently predicted by maternal weight (p=0.006), body mass index (p=0.001), and parity (p=0.012). CONCLUSION: In this nondiabetic/non-GDM cohort, maternal HOMA-IR was not associated with neonatal IR, body size or body composition. Larger studies are required to confirm these findings, with addi-tional inclusion of mothers with hyperglycaemia for comparison.

Depression Screening in Pediatric Orthopedic Surgery Clinics and Identifying Patients At-Risk.

BACKGROUND: Up to 25% of youth experience a depressive episode by 18 years of age, leading the US Preventive Services Task Force to recommend depression screening within this population. This study aimed to understand the prevalence of depression identified within pediatric orthopedic clinics compared with primary care clinics after the implementation of a screening program and present data on the prevalence of moderate-severe depression across specific pediatric orthopedic clinics, characterizing and identifying specific populations at higher risk. METHODS: A retrospective review was performed to identify all patients screened using the 2-item and 9-item versions of the Patient Health Questionnaire (PHQ-2/PHQ-9) and the Columbia-Suicide Severity Rating Scale over a 2-year period (October 2018 to January 2021) within pediatric primary care and orthopaedic clinics. Demographic and clinical characteristics were collected. Statistical analysis was performed to compare scores between orthopedic and primary care clinics, as well as between the different pediatric orthopedic subspecialties and included χ 2 test, ANOVA, and logistic regression. RESULTS: There were 32,787 unique adolescent patients screened in primary care clinics, with an additional 14,078 unique adolescent patients screened in orthopaedic clinics, leading to a 30% increase in the overall number of patients receiving depression screening. 5.2% of patients in primary care pediatric clinics screened positive for moderate-severe depression versus 2.0% in pediatric orthopaedic clinics ( P <0.001). 2.7% of primary care patients were at risk of self-harm compared with 0.8% of orthopedic patients ( P <0.001). Within orthopaedic subspecialty clinics, the spine patients were at the highest risk of moderate-severe depression (3.5%), significantly higher than both the sports (1.4%, P =0.006) and patients with acute fracture (1.3%, P <0.001). CONCLUSIONS: This study demonstrates the high incidence of patients screening positive for depression in pediatric and adolescent orthopaedic clinics. By identifying high-risk clinics and patient groups, health care systems can apply a more practical approach and appropriately deploy behavioral health specialists for timely counseling and treatment discussions. LEVEL OF EVIDENCE: Level-III.

3D analysis of the preoperative deformity in AIS can be used to guide surgical treatment decisions for selective thoracic fusion.

PURPOSE: To identify 3D measures of scoliosis from preoperative imaging that are associated with optimal radiographic outcomes after selective thoracic fusion (STF) for adolescent idiopathic scoliosis (AIS). METHODS: Subjects with primary thoracic curves (Lenke 1-4, B or C modifiers) fused selectively (L1 or above) who had preoperative 3D reconstructions and minimum 2 years of follow-up were included. An optimal outcome at 2 years was defined as having 4 of 5 parameters previously defined in the literature: (1) lumbar curve < 26º, (2) deformity flexibility quotient < 4, (3) C7-CSVL < 2 cm, (4) lumbar prominence < 5º and (5) trunk shift < 1.5 cm. Univariate and CART analyses were performed to identify preoperative variables associated with achieving an optimal outcome 2 years postoperatively. RESULTS: Ninety-nine (88F, 11 M) patients met inclusion. Mean age was 15 ± 2 years. Fifty-one subjects (52%) had an optimal outcome. Seven preoperative deformity measures representing smaller thoracolumbar/lumbar deformity in the optimal group were found to be significant on univariate analysis. CART analysis identified the following variables associated with optimal outcomes: difference in apical rotation > 30° = 27% optimal outcomes, difference in apical rotation ≤ 30° and coronal vertebral wedging of lumbar apex > 3° = 46% optimal outcomes, and difference in apical rotation ≤ 30° and coronal vertebral wedging of lumbar apex ≤ 3° = 80% optimal outcomes (p < 0.05). CONCLUSION: Optimal outcomes after STF were associated with a preoperative difference in apical vertebral rotation in the axial plane less than 30° between thoracic and lumbar curves as well as coronal plane vertebral wedging of the lumbar apical vertebra less than 3°.

Vertebral body tethering for Lenke 1A curves: the lumbar modifier predicts less optimal outcomes.

INTRODUCTION: The addition of the L4 "AR" and "AL" lumbar modifier for Lenke 1A idiopathic scoliosis (IS) has been shown to direct treatment in posterior spinal fusion; however, its utility in vertebral body tethering (VBT) has yet to be evaluated. METHODS: A review of a prospective, multicenter database for VBT in IS was performed for patients with Lenke 1A deformities and a minimum of 2 years follow-up. Patients were categorized by their lumbar modifier (AR vs AL). Less optimal VBT outcome (LOVO) was defined as a final coronal curve > 35°, lumbar adding-on, or revision surgery for deformity progression or adding-on. RESULTS: Ninety-nine patients met inclusion criteria (81% female, mean 12.6 years), with 55.6% being AL curves. Overall, there were 23 instances of tether breakage (23.3%) and 20 instances of LOVO (20.2%). There was a higher rate of LOVO in AR curves (31.8% vs 10.9%, P = 0.01). Patients with LOVO had greater preoperative deformity, greater apical translation, larger coronal deformity on first erect radiographs, and less coronal deformity correction. Failure to correct the deformity < 30° on first erect was associated with LOVO, as was LIV selection short of the last touch vertebra (TV). Independent risk factors for LOVO included AR curves (OR 3.4; P = 0.04) and first erect curve magnitudes > 30 degrees (OR 6.0; P = 0.002). DISCUSSION: There is a 20.2% rate of less optimal VBT following VBT for Lenke 1A curves. AR curves are independently predictive of less optimal outcomes following VBT and require close attention to LIV selection. Surgeons should consider achieving an initial coronal correction < 30 degrees and extending the LIV to at least the TV to minimize the risk of LOVO.

Validation of biomarkers of aging.

The search for biomarkers that quantify biological aging (particularly 'omic'-based biomarkers) has intensified in recent years. Such biomarkers could predict aging-related outcomes and could serve as surrogate endpoints for the evaluation of interventions promoting healthy aging and longevity. However, no consensus exists on how biomarkers of aging should be validated before their translation to the clinic. Here, we review current efforts to evaluate the predictive validity of omic biomarkers of aging in population studies, discuss challenges in comparability and generalizability and provide recommendations to facilitate future validation of biomarkers of aging. Finally, we discuss how systematic validation can accelerate clinical translation of biomarkers of aging and their use in gerotherapeutic clinical trials.

Prospectively Collected Comparison of Outcomes Between Surgically and Conservatively Treated Patients with Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective review of a prospectively collected multicenter registry. OBJECTIVE: To evaluate health-related quality of life (HRQOL) measures in an operative cohort of patients (OP) and compare them with a matched nonoperative cohort (NON). SUMMARY OF BACKGROUND DATA: Historically, the surgical outcomes of adolescent idiopathic scoliosis (AIS) have been radiographically evaluated. However, the importance of HRQOL measures and their impact on surgical outcomes are increasingly being understood. METHODS: We identified 90 NON patients with curves in the operative range who were observed for at least 2 years. These patients were matched with an OP cohort of 689 patients. All patients completed the Scoliosis Research Society-22 (SRS-22) questionnaire at the initial evaluation and at a minimum of 2-year follow-up. Subgroup comparisons were based on curve type: primary thoracic (Th), primary thoracolumbar/lumbar (TL/L), and double major (DM) curves. RESULTS: The preoperative major curves in the Th, TL/L, and DM OP subgroups averaged 50.4°, 45.4°, and 51.5°, respectively, and 49.4°, 43.7°, and 48.9° in the NON cohort (P > 0.05). At 2 years postoperatively, the major curve in the Th, TL/L, and DM OP subgroups improved to 19.0°, 19.2°, and 19.3°, respectively, compared to the progression to 51.3°, 44.5°, and 49.7° in the NON group at 2-year follow-up (P < 0.05). The SRS-22 self-image, mental health, satisfaction, and total scores at the 2-year follow-up were significantly better in all OP subgroups (P < 0.001) but remained largely unchanged in the NON group. A significant percentage of patients (P < 0.001) in the OP cohort reported better SRS-22 scores at the 2-year follow-up in the self-image, mental health, and satisfaction domains than the NON group at 2 years. CONCLUSIONS: Surgically treated patients with AIS have improved HRQOL outcomes in several domains compared to age- and curve magnitude-matched nonoperatively treated patients at 2-year follow-up.

Performance of MIL-101(Cr) and MIL-101(Cr)-Pore Expanded as Drug Carriers for Ibuprofen and 5-Fluorouracil Delivery.

Metal-organic frameworks (MOFs) have been extensively investigated as nanocarriers for drug delivery applications owing to their remarkable surface area and porosity, which allow for impregnation of large quantities of drugs with fast pharmacokinetics. In this work, we developed a pore-expanded version of MIL-101(Cr), MIL-101(Cr)-P, and assessed its potential as a carrier for ibuprofen and 5-fluorouracil drugs along with its regular MIL-101(Cr) analogue. The pore expansion strategy gave rise to a higher surface area and mesopore volume for MIL-101(Cr)-P relative to regular MIL-101(Cr). The characterization results revealed successful incorporation of 30, 50, and 80 wt % of both drugs within the MOF structure. Upon incorporation of species, the surface area and porosity of the two MOF carriers decreased drastically; however, the drug-loaded MOFs still retained some degree of porosity, even at high drug loadings. For both drugs, the delivery experiments conducted in phosphate-buffered saline (PBS) showed that MIL-101(Cr)-P possessed better pharmacokinetic behavior than MIL-101(Cr) by delivering higher amounts of drug at all three loadings and exhibiting much faster release rates. Such behavior was originated from large mesopores that were created during pore expansion, providing diffusional pathways for efficient delivery of the drugs. The highest rate constant obtained by fitting the release kinetics to the Higuchi model was found to be 0.44 h-1/2 for the release of 30 wt % 5-fluorouracil from MIL-101(Cr)-P. The findings of this study highlight the role of tuning physiochemical properties of MOFs in improving their pharmacokinetic behavior as drug carriers.