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To determine the outcomes of diagnostic and therapeutic arthroscopy in patients with chronic wrist pain who are younger than 16 years of age.We retrospectively analyzed collected data from medical records of patients who had undergone wrist arthroscopy by the senior author between 2015 and 2017 for longstanding wrist pain and were 16 years old or younger. Findings from preoperative magnetic resonance imaging (MRI) were compared with the intraoperative diagnosis, and midterm results were gathered by a telephone interview.Ten patients were included. Eight of 10 patients had undergone conservative therapy before surgery, and 60% had a history of single trauma. In 6 of 10 patients, the arthroscopic diagnosis correlated with the MRI findings. Eight of 10 wrists (80%) showed a tear of the triangular fibrocartilage complex (TFCC). Only 4 of the 8 TFCC tears were correctly identified by 3-Tesla MRI.In our study, wrist arthroscopy was an effective tool not only to diagnose but also to treat relevant TFCC lesions both in adolescents and children suffering from persistent wrist pain. A 3-Tesla MRI was neither sensitive nor specific enough to correctly diagnose lesions in small pediatric wrists.IV, Therapeutic case series.

Perinatal Psychiatry Access Programs ("Access Programs") are system-level interventions that aim to build the capacity of perinatal healthcare professionals to address mental health, and thereby improve access to perinatal mental healthcare. Access Programs are widely implemented and positioned to promote health equity in perinatal mental healthcare, but little is known about the adaptations being made to the model in response to calls to promote health equity.One respondent from each of the 14 Access Programs (n = 14) completed an online survey that queried on adaptations made to promote perinatal mental healthcare equity.Twelve of the 14 Access Program team members (86%) indicated implementation of at least one new equity initiative. The average number of initiatives that a single Access Program implemented was 3.5 (range 0-10). Two Access Programs (14%) implemented 8.5 initiatives (range: 7-10), indicating that a small cohort is leading promotion of equity among Access Programs.Efforts to further expand the capacity and services of Access Programs to address perinatal mental healthcare inequities are needed. These adaptations may provide a robust opportunity for implementation initiatives to promote health equity through a system-level intervention.

Fatty acids (FA) play an important role in health and heart disease risk.We evaluated relationships of plasma FA levels, especially omega-3 FA, with sex, age, and reported heart disease mortality rates by state in a very large clinical population.Plasma FA were measured by gas chromatography/mass spectrometry after lipid extraction in 1,169,621 fasting United States subjects grouped according to sex (56.2% female), age (30, 30-45, 45-55, 55-65, ≥65 years; median age 58.2 years), and state of residence.Plasma FA index values (median±interquartile range), expressed as a percent of total plasma FA, in all subjects were: saturated (14:0+16:0+18:0) 31.4±1.5%; monounsaturated (16:1n7-cis+18:1n9-cis) 21.3±2.2%; trans (16:1n7-trans+18:1n9-trans) 0.45±0.08%; omega-6 (18:2n6-cis+20:3n6+20:4n6) 42.5±3.0%; and omega-3 (20:5n3+22:6n3) 2.57±0.81%. The median eicosapentaenoic acid (EPA, 20:5n3) concentration was 22.1±9.7 μg/mL. Females had significantly (P0.0001) higher omega-3 FA indices (+6.82%) than males. Subjects ≥65 years of age had a higher omega-3 FA index (+29.68%) and higher EPA levels (+57.05%) than subjects30 years of age (P0.00001). EPA concentrations and omega-3 FA indices were below overall median levels in most southern and midwestern states. State-reported heart disease mortality rates were inversely correlated with EPA levels (r=-0.504) and omega-3 FA indices (r=-0.570), and positively correlated with saturated FA indices (r=0.450), all P0.01.In our large population, females, subjects ≥65 years, and those living in northeastern and western states had higher omega-3 fatty acid levels and lower saturated fatty acid levels than other subjects. Such changes were associated with lower state-wide heart disease death rates.

The Covid 19 pandemic has caused dramatic disruptions in the public transport sector that has seen a stark downturn in many cities across the globe, calling into question previous efforts to reduce air pollution and CO2 emissions by expanding this sector. Especially, the current surge of individual car use is worrying and the question remains which users might be able and willing to substitute public transport by cycling. This effect is interesting to study for the case of Hanover Region, because of the well-developed biking infrastructure that makes biking a viable alternative to individual car use. In this paper, we analyze survey data from June 2020 on the use of transportation modes before and during the pandemic in the Hanover Region. We ask if and how the over 4.000 participants substitute public transport and what characterizes those who chose biking over individual car use. We use multivariate regression models and find evidence that Stadtbahn (local light rail) and bus are substituted by bike, car and working from home, while train use is not significantly replaced by car and seems to be positively related to bike use. The data also shows that women have a higher level of fear of infection than men have during public transport use and therefore reduce public transport use more. Moreover, income displays a positive effect on increased car use while cycling is independent of socio-economic indicators but instead driven by the eco-consciousness of users. Surprisingly, we find that car use was increased in particular by residents of Hanover city, while it was decreased by residents of less densely populated urban areas in the region.

Introduction Fracture-related infection (FRI) is a severe post-traumatic complication which is occasionally accompanied by a deficient or even avital soft-tissue envelope. In these cases, a thoroughly planned orthoplastic approach is imperative as a vital and intact soft-tissue envelope is mandatory to achieve fracture union and infection eradication. The aim of this study was, to analyse if soft-tissue reconstruction (STR) without complications is associated with a better long-term outcome compared to FRI patients with STR complications. In particular, it was investigated if primary flap failure represented a risk factor for compromised fracture union and recurrence of infection. Patients and Methods Patients with a lower leg FRI requiring STR (local, pedicled and free flaps) who were treated from 2010-18 at the University Hospital Basel were included in this retrospective analysis. The main outcome measure was the success rate of STR, further outcome measures were fracture nonunion and recurrence of infection. Results Overall, 145 patients with lower leg FRI were identified, of whom 58 (40%) received STR (muscle flaps: n��=��38, fascio-cutaneous flaps: n=19; composite osteo-cutaneous flap: n��=��1). In total seven patients required secondary STR due to primary flap failure. All failures and flap-related complications occurred within the first three weeks after surgery. Secondary STR was successful in all cases. A high Charlson Comorbidity Index Score was a significant risk factor for flap failure (p��=��0.011). Out of the 43 patients who completed the 9-month follow-up, 11 patients presented with fracture nonunion and 12 patients with a recurrent infection. Polymicrobial infection was a significant risk factor for fracture nonunion (p��=��0.002). Primary flap failure was neither a risk factor for compromised fracture consolidation (p��=��0.590) nor for recurrence of infection (p��=��0.508). Conclusion: A considerable number of patients with lower-leg FRI required STR. This patient subgroup is complex and rich in complications and the long-term composite outcome demonstrated a high rate of compromised fracture consolidation and recurrent infections. It appears that secondary STR should be performed, as primary flap failure was neither a risk factor for compromised fracture consolidation nor for recurrence of infection. We propose to monitor these patients closely for three weeks after STR.

In this paper, we analyze how sequentially introducing decision variables into an integer program (IP) affects the value function and its level sets. We use a Gilmore-Gomory approach to find parametrized IP value functions over a restricted set of variables. We introduce the notion of maximal connected subsets of level sets - volumes in which changes to the constraint right-hand side have no effect on the value function - and relate these structures to IP value functions and optimal solutions.

Purpose To evaluate clinical outcomes and patient-reported outcomes of patients who underwent primary anterior cruciate ligament (ACL) repair using suture tape augmentation. Methods Patients with a proximal tear of the ACL who underwent primary ACL repair with a minimum 2-year follow-up were included. The exclusion criteria included multiligamentous knee injuries, midsubstance tears, tibial avulsion fractures, and distal tears. Demographic characteristics, injury pattern, concomitant injury pattern, and patient-reported outcome measures were recorded. Patients were evaluated at a minimum 2-year follow-up for clinical success, defined as stability not requiring revision ACL reconstruction, and for patient-reported outcome measurements. Failure was defined as the need for revision surgery. Results The mean follow-up period was 2.8 ± 0.9 years. Thirty-five patients met the inclusion criteria, with an average age of 32.2 ± 7.2 years, and 2-year follow-up was obtained for 29 of these patients. Revision surgery was required in 2 of the 29 patients (6.9%); successful treatment was achieved in the remaining 93.1%. The Single Assessment Numeric Evaluation score and Knee Injury and Osteoarthritis Outcome Score for the 27 successfully treated patients were recorded, with 70.4% having Single Assessment Numeric Evaluation scores of 80 or greater. Conclusions This case series shows that primary surgical repair of proximal ACL tears using suture tape augmentation results in a low rate of revision surgery. Level of Evidence Level IV, prospective case series.

High-quality genomic tools have been integral in understanding genomic architecture and function in the modern-day horse. The equine genetics community has a long tradition of pooling resources to develop genomic tools. Since the equine genome was sequenced in 2006, several iterations of high throughput genotyping arrays have been developed and released, enabling rapid and cost-effective genotyping. This review highlights the design considerations of each iteration, focusing on data available during development and outlining considerations in selecting the genetic variants included on each array. Additionally, we outline recent applications of equine genotyping arrays as well as future prospects and applications.

We study when a facet-defining inequality for a deterministic, single-scenario subproblem is also facet-defining for the extensive form of a two-stage stochastic mixed-integer linear program (SMIP). To answer this question, we introduce a novel stochastic variant of the well-known single-node flow (SNF) polytope, and present necessary and sufficient conditions for single-scenario facet-defining inequalities to be facet-defining for the extensive form. We further demonstrate that our stochastic SNF polytope is a relaxation of a broad subclass of SMIPs, illustrating its generality.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused over 6 million deaths world-wide. In the pre-vaccination era, we noted a 5·3% SARS-CoV-2 IgG antibody positivity rate in 81,624 subjects.Utilizing assays for serum SARS-CoV-2 spike (S) protein antibody (Roche) and neutralizing antibody (Diazyme), both90% IgG, we measured antibodies in 13,189 subjects in the post-vaccination era, and in 69 subjects before and 60 days after booster vaccination.In 2021, in 10,267 subjects, 25·0% had negative S protein levels (0.80 U/L), 24·4% had low positive levels (0.80-250 U/L), and 50·7% had high positive levels (250 U/L). Median neutralizing antibody levels were 1·16 and 2·06 AU/mL in the low and high positive groups, respectively. In 2022, we evaluated 2,016 subjects where samples were diluted 1:100 if S protein antibody levels were250 U/L. Median S protein and neutralizing antibody levels were 2,065 U/L (86.3% positivity) and 2·68 AU/mL (68.0% positivity), respectively. Antibody levels were also measured in 69 subjects before and 60 days after receiving SARS-CoV-2 booster vaccinations. Treatment resulted in a 15-fold increase in S protein antibody levels from 1,010 to 17,236 U/L, and a 6-fold increase in neutralizing antibody from 1·51 to 12·51 AU/mL in neutralizing antibody levels, respectively (bothOur data indicate that by early 2022 86% of subjects had positive SARS-CoV-2 S protein antibody levels, and that these levels and neutralizing antibody levels were increased 15-fold and 6-fold, respectively, 60 days after SARS-Cov-2 booster vaccination.

Engineering of materials consisting of hypertrophic cartilage, as physiological template for de novo bone formation through endochondral ossification (ECO), holds promise as a new class of biological bone substitutes. Here, we assessed the efficiency and reproducibility of bone formation induced by the combination of ceramic granules with fractionated human adipose tissue (“nanofat”), followed by in vitro priming to hypertrophic cartilage. Human nanofat was mixed with different volumetric ratios of ceramic granules (0.2-1 mm) and cultured to sequentially induce proliferation (3 weeks), chondrogenesis (4 weeks), and hypertrophy (2 weeks). The resulting engineered constructs were implanted ectopically in nude mouse. The presence of ceramic granules regulated tissue formation, both in vitro and in vivo. In particular, their dispersion in nanofat at a ratio of 1:16 led to significantly increased cell number and glycosaminoglycan accumulation in vitro, as well as amount and inter-donor reproducibility of bone formation in vivo. Our findings outline a strategy for efficient utilization of nanofat for bone regeneration in an autologous setting, which should now be tested at an orthotopic site. Statement of significance In this study, we assessed the efficiency and reproducibility of bone formation by a combination of ceramic granules and fractionated human adipose tissue, also known as nanofat, in vitro primed into hypertrophic cartilage. The resulting engineered cartilaginous constructs, when implanted ectopically in nude mouse, resulted in bone and bone marrow formation, more reproducibly and strongly that nanofat alone. This project evaluates the impact of ceramic granules on the functionality and chondrogenic differentiation of mesenchymal progenitors inside their native adipose tissue niche and outlines a novel strategy for an efficient application of nanofat for bone regeneration in an autologous setting.

Preoperative imaging by Computed Tomographic Angiography (CTA) has been promoted a gold standard tool for perforator mapping in abdominally based microsurgical breast reconstruction, while Color Doppler Ultrasound (CDU) has lost its popularity. As the CTA X-ray exposure might have long-term consequences for patients, CDU has regained importance for preoperative workup in our center. Our aim was to revisit the role of CDU by comparing the reliability of CDU and CTA in predicting intraoperative perforator selection.We performed a retrospective chart review study of patients who underwent microsurgical breast reconstructions with DIEP flaps at our institution. Both CTA and CDU were performed prior to the surgery, and both imaging entities were thoroughly examined by the surgical team. Perforator identification, number, size, and location were assessed and correlated with CTA and CDU data and with intraoperative findings.We identified 98 patients who received 125 DIEP flap surgeries. A significantly stronger correlation was found between CDU and intraoperative findings of perforator detection and size (p0.0001) and selection (r = 0.9987, CI 0.9981-0.9991, p 0.0001 and r = 0.01, CI -0.18-0.2, p = 0.91, respectively), when compared with CTA data. If none of the preoperative imaging studies matched intraoperative perforator selection, an association with a higher incidence of flap loss (Odds ratio 4.483, CI 0.5068-39.65, p = 0.2171) was found.Our data suggests that CDU might regain relevance as a safe and reliable preoperative imaging study, without the risk and potential consequences of X-ray exposure. Preoperative imaging tools like CDU and CTA should be considered part of the gold standard in abdominally based free flap breast reconstruction.

Background Changes in body mass index (ΔBMI) have well-established relationships to changes in high-density lipoprotein (ΔHDL)-cholesterol concentrations; however, their relationships to ΔHDL subfractions are less well understood. Objective Assess the associations between ΔHDL and ΔBMI in a very large cohort. Method Age and sex-adjusted Δapo A1 concentrations were measured within 10 HDL subfractions in 14,121 women and 13,969 men using two-dimensional HDL-mapping. Significance was identified at .01 Results ΔBMI was significantly associated with Δα-1 (very large HDL, slope ± SE, females: −0.39 ± 0.07§; males: −0.51 ± 0.05§), Δα-3 (medium HDL, females: 0.18 ± 0.04§; males: 0.19 ± 0.04§), and Δα-4 (small HDL, females: 0.14 ± 0.03§; males: 0.15 ± 0.04§ mg/dL per kg/m2). As a percent of baseline, the changes in α-1 per ΔBMI were nearly twice as great as the changes in HDL-cholesterol per ΔBMI in both males (−1.53% vs −0.77%) and females (−0.79% vs −0.42%). HDL-cholesterol decreased significantly in healthy-weight patients who became overweight, overweight patients who became class I or class II obese, class I obese patients who became class II obese, and class II obese patients who became class III. In contrast, HDL-cholesterol increased in class III obese patients who became class II or class I, class II obese patients who became class I or overweight, class I patients who became overweight or healthy weight, overweight patients who became healthy weight, and healthy weight patients who became underweight. Conclusions Weight change significantly affects HDL-cholesterol concentrations throughout the obesity spectrum. ΔBMI's effect on Δα-1 was nearly twice as great as its effect on HDL-cholesterol.

SARS-CoV-2 has infected millions worldwide. The virus is novel, and currently there is no approved treatment. Convalescent plasma may offer a treatment option. We evaluated trends of IgM/IgG antibodies/plasma viral load in donors and recipients of convalescent plasma. 114/139 (82 %) donors had positive IgG antibodies. 46/114 donors tested positive a second time by NP swab. Among those retested, the median IgG declined (p < 0.01) between tests. 25/139 donors with confirmed SARS-CoV-2 were negative for IgG antibodies. This suggests that having had the infection does not necessarily convey immunity, or there is a short duration of immunity associated with a decline in antibodies. Plasma viral load obtained on 35/39 plasma recipients showed 22 (62.9 %) had non-detectable levels on average 14.5 days from positive test versus 6.2 days in those with detectable levels (p < 0.01). There was a relationship between IgG and viral load. IgG was higher in those with non-detectable viral loads. There was no relationship between viral load and blood type (p = 0.87) or death (0.80). Recipients with detectable viral load had lower IgG levels; there was no relationship between viral load, blood type or death.

We assessed secondary and genetic causes of severe HDL deficiency in 258,252 subjects, of whom 370 men (0.33%) and 144 women (0.099%) had HDL cholesterol levels G; 2) LCAT (12.4%): 1 homozygote, 3 compound heterozygotes, 13 heterozygotes, and 8 heterozygotes with variant rs4986970/p.S232T; 3) APOA1 (5.0%): 1 homozygote and 9 heterozygotes; and 4) LPL (4.5%): 1 heterozygote and 8 heterozygotes with variant rs268/p.N318S. In addition, 4.5% had other mutations, and 46.8% had no mutations. Atherosclerotic cardiovascular disease (ASCVD) prevalence rates in the ABCA1,LCAT,APOA1, LPL, and mutation-negative groups were 37.0%, 4.0%, 40.0%, 11.1%, and 6.4%, respectively. Severe HDL deficiency is uncommon, with 40.1% having secondary causes and 48.8% of the subjects sequenced having ABCA1,LCAT,APOA1, or LPL mutations or variants, with the highest ASCVD prevalence rates being observed in the ABCA1 and APOA1 groups.

The Central Andes of South America boasts a rich history of complex societies and sophisticated economic networks. Reconstructing patterns of diet across time is important to understanding the relationships between subsistence and food preparation and their roles in mediating consumption and hegemony through time. The region surrounding the city of Cusco in the southern Peruvian highlands is best known as the heartland of the Inca Empire (520-418 BP); however, it has a long history of social complexity and regional exchange, including colonization by the highland Wari Empire (1350-950 BP) and in situ development in earlier periods. Elucidating subsistence and mobility over time in the Cusco region is therefore essential for reconstructing the evolution of complex Andean polities and their effects on local communities. This study presents carbon, nitrogen, and oxygen isotopic data from human bone and tooth enamel at four Cusco-region sites: the hunter-gatherer site of Kasapata (6350- 4150 BP, N = 8); the village site of Yuthu (2350-2050 BP, N = 22); the Wari colony of Hatun Cotuyoc (1350-950 BP, N = 9) and the contemporaneous village site of Ak'awillay (N = 22). Key aims are to estimate diachronic shifts in foodways and nutrition, and those related to Wari control. Results indicate nearly-identical isotope values at Kasapata and Yuthu trending toward lower-trophic level C3 proteins and C3 energy sources, while values indicate mixed C3/C4 diets at Ak'awillay and diets dominated by terrestrial meat and C4 foods at Hatun Cotuyoc. Interestingly, oxygen isotope values suggest water source variation consistent with minimal mobility at Kasapata and regional mobility at Yuthu, but possibly with overlapping but divergent foodways at Ak'awillay and Hatun Cotuyoc resulting in differential evaporative pressures on consumed water rather than increased mobility.

Many steps are required to generate bone through endochondral ossification with adipose mesenchymal stromal cells (ASC), from cell isolation to in vitro monolayer expansion, seeding into scaffolds, cartilaginous differentiation and in vivo remodeling. Moreover, monolayer expansion and passaging of ASC strongly decreases their differentiation potential. Here, we propose that adipose tissue itself can be used as scaffold for ASC expansion and endochondral ossification. Human liposuctions were fractionated and cultured for 3 weeks with proliferative medium in suspension. The resulting constructs, named Adiscaf, were compared to constructs generated with a previously developed, control approach, i.e. collagen sponges seeded with monolayer-expanded ASC. After 4 weeks of chondrogenic differentiation, Adiscaf contained cartilage tissue, characterized by glycosaminoglycans and collagen type II. After 2 additional weeks of hypertrophic differentiation, Adiscaf showed upregulation of hypertrophic markers at the gene expression and protein levels. After 8 weeks of in vivo implantation, Adiscaf resulted in ectopic bone tissue formation, including bone marrow elements. Adiscaf showed superior in vitro differentiation and in vivo performance as compared to the control paradigm involving isolation and monolayer expansion of ASC. This new paradigm exploits the physiological niche of adipose tissue and strongly suggests a higher functionality of cells inside adipose tissue after in vitro expansion. This study demonstrates that adult human adipose tissue used as a native construct can generate a bone organ by endochondral ossification. The concept could be exploited for the generation of osteogenic grafts for bone repair. Statement of Significance In this study we used adult human adipose tissue as scaffolding materials (called Adiscaf) to generate a bone organ by endochondral ossification. Adiscaf concept is based on the culture of adipose tissue cells inside their native microenvironment for the generation of osteogenic grafts for bone repair. This simplified approach overcomes several limitations linked to the current techniques in bone tissue engineering, such as isolation of cells and inadequate properties of the biomaterials used as scaffolds. In addition, the present paradigm proposes to exploit physiological niches in order to better maintain the functionality of cells during their in vitro expansion. This project not only has a scientific impact by evaluating the impact of native physiological niches on the functionality and chondrogenic differentiation of mesenchymal progenitors but also a clinical impact to generate osteogenic grafts and/or osteoinductive materials for bone regeneration and repair.

The noble elements, argon and xenon, are frequently employed as the target and event detector for weakly interacting particles such as neutrinos and Dark Matter. For such rare processes, background radiation must be carefully minimized. Radon provides one of the most significant contaminants since it is an inevitable product of trace amounts of natural uranium. To design a purification system for reducing such contamination, the adsorption characteristics of radon in nitrogen, argon, and xenon carrier gases on various types of charcoals with different adsorbing properties and intrinsic radioactive purities have been studied in the temperature range of 190-295 K at flow rates of 0.5 and 2 standard liters per minute. Essential performance parameters for the various charcoals include the average breakthrough times ($\tau$), dynamic adsorption coefficients (k$_a$) and the number of theoretical stages (n). It is shown that the k$_a$-values for radon in nitrogen, argon, and xenon increase as the temperature of the charcoal traps decreases, and that they are significantly larger in nitrogen and argon than in xenon gas due to adsorption saturation effects. It is found that, unlike in xenon, the dynamic adsorption coefficients for radon in nitrogen and argon strictly obey the Arrhenius law. The experimental results strongly indicate that nitric acid etched Saratech is the best candidate among all used charcoal brands. It allows reducing total radon concentration in the LZ liquid Xe detector to meet the ultimate goal in the search for Dark Matter., Comment: 11 pages, 10 figures

Cerebrotendinous xanthomatosis (CTX) is a rare disorder due to defective sterol 27-hydroxylase causing a lack of chenodeoxycholic acid (CDCA) production and high plasma cholestanol levels.Our objective was to review the diagnosis and treatment results in 43 CTX cases.We conducted a careful review of the diagnosis, laboratory values, treatment, and clinical course in 43 CTX cases.The mean age at diagnosis was 32 years; the average follow-up was 8 years. Cases had the following conditions: 53% chronic diarrhea, 74% cognitive impairment, 70% premature cataracts, 77% tendon xanthomas, 81% neurologic disease, and 7% premature cardiovascular disease. The mean serum cholesterol concentration was 190 mg/dL; the mean plasma cholestanol level was 32 mg/L (normal5.0 mg/L), which decreased to 6.0 mg/L (-81%) with CDCA therapy generally given as 250 mg orally 3 times daily. Of those tested on treatment, 63% achieved cholestanol levels of5.0 mg/L; 91% had normal liver enzyme levels; none had significant liver problems after dose adjustment. Treatment improved symptoms in 57% at follow-up, but 20% with advanced disease continued to deteriorate. In the United States, CDCA has been approved for gallstone dissolution, but not for CTX despite long-term efficacy and safety data.Health care providers seeing young patients with tendon xanthomas and relatively normal cholesterol levels, especially those with cataracts and learning problems, should consider the diagnosis of CTX so they can receive treatment. CDCA should receive regulatory approval to facilitate therapy for the prevention of the complications of the disease.

Despite the various reported approaches to generate osteochondral composites by combination of different cell types and materials, engineering of templates with the capacity to autonomously and orderly develop into cartilage-bone bi-layered structures remains an open challenge. Here, we hypothesized that the embedding of cells inducible to endochondral ossification (i.e. bone marrow derived mesenchymal stromal cells, BMSCs) and of cells capable of robust and stable chondrogenesis (i.e. nasal chondrocytes, NCs) adjacent to each other in bi-layered hydrogels would develop directly in vivo into osteochondral tissues. Poly(ethylene glycol) (PEG) hydrogels were functionalized with TGFβ3 or BMP-2, enzymatically polymerized encapsulating human BMSCs, combined with a hydrogel layer containing human NCs and ectopically implanted in nude mice without pre-culture. The BMSC-loaded layers reproducibly underwent endochondral ossification and generated ossicles containing bone and marrow. The NC-loaded layers formed cartilage tissues, which (under the influence of BMP-2 but not of TGFβ3 from the neighbouring layer) remained phenotypically stable. The proposed strategy, resulting in orderly connected osteochondral composites, should be further assessed for the repair of osteoarticular defects and will be useful to model developmental processes leading to cartilage-bone interfaces.

Given a set of feasible solutions X to a linear program, we study the set of objectives that make X optimal, known as the inverse-feasible region. We show the relationship between the dimension of a face of a polyhedron and the dimension of the corresponding inverse-feasible region, which leads to necessary and sufficient conditions of the extreme, boundary, and inner points of a linear program. We also characterize the set of objectives that render a given solution uniquely optimal.

Background:Helicobacter pylori infection is a known risk factor for duodenal ulcers, gastritis, and gastric cancer. The eradication of H. pylori is successful in treating these disorders; however, the success rate of eradication therapy is declining. There may be an interaction with nutrient intake to account for this decline.Objective: We investigated the influence of food and nutrient intake on H. pylori eradication therapy.Design: In this study, 4014 subjects underwent endoscopy, were tested for serum antibodies to H. pylori (2046 positive; 51.0%), and had their food intake assessed with the use of a food-frequency questionnaire (FFQ). Of the positive subjects, endoscopies showed that 389 (19.0%) had gastritis and/or duodenal ulcers and were also positive for a 13C-urea breath test (UBT). These 389 subjects received 1-wk H. pylori eradication therapy with lansoprazole, amoxicillin, and clarithromycin and a second UBT 8 wk after treatment. Complete demographic characteristics, serum lipid, insulin, glycated hemoglobin, C-reactive protein (CRP), and creatinine concentrations as well as complete FFQs were available for 352 subjects. Multivariate logistic regression analyses were performed to determine factors that were associated with successful H. pylori eradication therapy.Results: The success rate of eradication therapy was 60.4% (235 of 389). Factors associated with the failure of eradication therapy included increased age (P = 0.02), higher CRP concentrations (P < 0.01), higher dietary cholesterol (P < 0.01) or egg intake (P < 0.01), higher ω-3 (n-3) fatty acid (P = 0.02) or fish intake (P = 0.01), and higher vitamin D intake (P = 0.02). Moreover, the higher vitamin D intake was strongly linked to higher fish intake. A limitation of the study is that we did not assess the antibiotic resistance of H. pyloriConclusions: Our results indicate that higher egg and fish intake may be negatively correlated with successful H. pylori eradication therapy in H. pylori-positive subjects with gastritis and/or duodenal ulcers.

Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride-rich lipoproteins (TRLs), lbLDL (density [d] = 1.019–1.044 g/ml), and sdLDL (d = 1.044–1.063 g/ml) were determined in the fed state by using stable isotope tracers, mass spectrometry, and compartmental modeling. Compared with placebo, rosuvastatin decreased LDL cholesterol and apoB-100 levels in TRL, lbLDL, and sdLDL by significantly increasing the fractional catabolic rate of apoB-100 (TRL, +45%; lbLDL, +131%; and sdLDL, +97%), without a change in production. On placebo, 25% of TRL apoB-100 was catabolized directly, 37% was converted to lbLDL, and 38% went directly to sdLDL; rosuvastatin did not alter these distributions. During both phases, sdLDL apoB-100 was catabolized more slowly than lbLDL apoB-100 (P < 0.01). Proteomic analysis indicated that rosuvastatin decreased apoC-III and apoM content within the density range of lbLDL (P < 0.05). In our view, sdLDL is more atherogenic than lbLDL because of its longer plasma residence time, potentially resulting in more particle oxidation, modification, and reduction in size, with increased arterial wall uptake. Rosuvastatin enhances the catabolism of apoB-100 in both lbLDL and sdLDL.

Summary Objective The popularity of the superficial circumflex iliac artery perforator (SCIP) flap has been limited by factors such as variable vascular anatomy and short arterial pedicle. This article aimed to delineate flap design and harvest strategies based around either the proximal or distal perforators of the superficial circumflex iliac artery (SCIA) and propose a set of strategies that can help deal with the limitations of the flap. Method From August 2011 to June 2015, the SCIP flap was used in 80 patients for soft tissue defects at our institution. We utilized vessel imaging navigation to get a detailed overview of the vascular anatomy preoperatively. Flaps were designed on the basis of either the proximal or distal perforators of the SCIA. Backup strategies and surgical maneuvers were suggested to solve the problems that emerged during surgery. Results In total, 51 flaps were raised on the basis of the proximal perforators of the superficial branch of the SCIA, whereas 25 cases were based on the distal perforators from the deep branch, and in four cases, the pedicle was switched to the superficial inferior epigastric artery. In eight cases, the arterial pedicle lengthen technique was applied with a maximum length of 10 cm. All donor sites were closed directly with inconspicuous scars. Conclusion These surgical strategies simplified the intraoperative decision-making and overcame the shortcomings of the SCIP flap. We believe that the SCIP flap has a great potential to become a new workhorse flap in the field of reconstructive surgery.

This study explores two potential safeguards against liability when auditors exercise professional skepticism, but do not detect a fraud: (1) a firm policy requiring a specific level of professional skepticism in high-risk audit areas and (2) providing jurors with key differences between the role of a fraud examiner and the role of an auditor as a reference point for judging the auditor’s performance. We find that describing a specific firm policy to jurors does not significantly decrease negligence findings for auditors who do not detect a fraud. However, providing the role of a fraud examiner as a reference point (e.g., scope of work, testing approaches) does significantly decrease negligence findings. Encouragingly, we also find some evidence that jurors are apt to decrease negligence findings when auditors exercise higher skepticism, but ultimately do not detect a fraud.

SARS-CoV-2 has infected millions worldwide. Convalescent plasma may offer a treatment option. We evaluated trends of IgM/IgG antibodies/plasma viral load in donors and recipients of convalescent plasma. 114/139 (82%) donors had positive IgG antibodies. 46/114 donors tested positive a second time by NP swab. Among those retested, the median IgG declined (p

Introduction The opioid epidemic remains a challenging problem currently facing healthcare systems. As opioids are often prescribed in greater quantities than patients consume, proper disposal of unused medications is crucial. Identification of the problem Literature suggests many patients who are prescribed opioids share medications with another person and that there is a lack of patient education regarding safe disposal of opioids. Purpose of the Study To analyze how the implementation of the Deterra® Disposal Pouch (DDP), and education regarding its use, may reduce the percentage of improper disposals of opioids following orthopedic surgery. Secondly, the study examined the patient utilization rate of the DDP after implementation. Methodology All patients undergoing elective orthopedic surgery at a single ambulatory surgery center noted their opioid disposal technique via an automated survey 2-weeks post-operatively. Pre-implementation (12/2018-02/2019) versus post-implementation (12/2019-02/2020) of the DDP were compared for improper disposal (storing prescription, flushing down the toilet, etc.) versus proper disposal (DDP, dropped at police station/pharmacy/city-hall, etc.). Patients not prescribed opioids, still taking opioids, or who had finished their opioid prescription at the time of the survey were excluded. Results Prior to implementation of the DDP, 54.2% (n=39) of patients disposed of their opioids improperly versus 45.8% (n=33) properly. Following implementation, 49.1% (n=53) disposed of their opioids improperly versus 50.9% (n=55) properly. Importantly, post-implementation, 21.3% (n=23) of patients disposed of their opioids using the DDP. This difference between 54.2% and 49.1% was not statistically significant, yet may be deemed clinically relevant (p=.502). Discussion The results suggest the effectiveness of implementing strategies to encourage proper disposal of unused opioids following orthopedic surgery, with important implications for reducing the negative, secondary effects of improperly storing and disposing of opioids. Conclusion Comprehensive implementation and education regarding proper use of the DDP led to decreases in improper opioid disposal, with over 1 in 5 patients utilizing the new disposal method. Implications for perianesthesia nurses and future research Perianesthesia nurses play an important role in educating patients about correct use and reasoning behind proper disposal of opioids. The authors recognize this data is preliminary, but further large-scale studies are warranted to study effective opioid disposal.

The precise time, the original location, and the processes involved in the creation of Germany’s capital Berlin are still unknown due to a lack of surviving documents. As such, archaeology and bioarchaeology play a critical role in understanding the people who lived in medieval Berlin. In this paper, we describe an isotope analysis aimed at identifying what the early inhabitants of Berlin were eating and at inferring dietary variation among skeletons sexed as male versus female, and among those interred before and after the Yersinia pestis pandemic known as the Black Death (1347–1352 CE). Carbon (δ13C) and nitrogen (δ15N) isotope ratios from 66 skeletons from the medieval cemetery site of Petriplatz indicate that males consumed proportionately more protein than females before the Black Death. However, a significant increase in δ15N values in skeletons associated with post-Black Death contexts suggests an increased consumption of animal protein for both males and females. This study is the first dietary isotopic analysis to be conducted on the skeletons at Petriplatz and is only the second paleodietary isotopic reconstruction of the High Middle Ages in Germany. Consequently, this study provides key insights into the cultural responses to the ecology of the Black Death by the people of Berlin within the broader context of medieval Germany and medieval Europe.

Background Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the primary omega-3 fatty acids in fish oil, have been shown to reduce cardiovascular disease (CVD) risk. Objective This study aimed to examine the independent effects of EPA and DHA on lipid and apolipoprotein levels, as well as on inflammatory biomarkers of CVD risk, using doses often used in the general population. Design A blinded, randomized 6-week trial was performed in 121 healthy, normolipidemic subjects who received olive oil placebo 6g/d, EPA 600mg/d, EPA 1800mg/d, or DHA 600mg/d. The EPA was derived from genetically modified yeast. Results The subjects tolerated the supplements well with no safety issues; and the expected treatment-specific increases in plasma EPA and DHA levels were observed. Compared to placebo, the DHA group had significant decreases in postprandial triglyceride (TG) concentrations (−20%, −52.2mg/dL, P=0.03), significant increases in fasting and postprandial low-density lipoprotein cholesterol (LDL-C) (+18.4%, 17.1mg/dL, P=0.001), with no significant changes in inflammatory biomarkers. No significant effects were observed in the EPA 600mg/d group. The high-dose EPA group had significant decreases in lipoprotein-associated phospholipase A2 concentrations (Lp-PLA 2 ) (−14.1%, −21.4ng/mL, P=0.003). Conclusions The beneficial effects of EPA 1800mg/d on CVD risk reduction may relate in part to the lowering of Lp-PLA 2 without adversely affecting LDL-C. In contrast, DHA decreased postprandial TG, but raised LDL-C. Our observations indicate that these dietary fatty acids have divergent effects on cardiovascular risk markers.

Summary Background Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. Methods In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2–6 cm 2 ) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. Findings For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage. Interpretation Hyaline-like cartilage tissues, engineered from autologous nasal chondrocytes, can be used clinically for repair of articular cartilage defects in the knee. Future studies are warranted to assess efficacy in large controlled trials and to investigate an extension of indications to early degenerative states or to other joints. Funding Deutsche Arthrose-Hilfe.

Background Lipoprotein lipase (LPL) is a multifunctional protein and a key enzyme involved in the regulation of lipoprotein metabolism. We determined the lipoproteins to which LPL is bound in the pre-heparin and post-heparin plasma. Methods Tetrahydrolipstatin (THL), a potent inhibitor of serine lipases, was used to block the lipolytic activity of LPL, thereby preventing changes in the plasma lipoproteins due to ex vivo lipolysis. Gel filtration was performed to obtain the LPL elution profiles in plasma and the isolated remnant lipoproteins (RLP). Results When ex vivo lipolytic activity was inhibited by THL in the post-heparin plasma, majority of the LPL was found in the VLDL elution range, specifically in the RLP as inactive dimers. However, in the absence of THL, most of the LPL was found in the HDL elution range as active dimers. Furthermore, majority of the LPL in the pre-heparin plasma was found in the RLP as inactive form, with broadly diffused lipoprotein profiles in the presence and absence of THL. Conclusions It is suggested that during lipolysis in vivo , the endothelial bound LPL dimers generates RLP, forming circulating RLP-LPL complexes in an inactive form that subsequently binds and initiates receptor-mediated catabolism.

ObjectivesLipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a).Materials and methodsThe kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9-124.7nmol/L]. All subjects received a primed constant infusion of [5,5,5-(2)H3] L-leucine while in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma; apo(a) and apoB-100 were separated by gel electrophoresis; and isotopic enrichment was determined by gas chromatography/mass spectrometry.ResultsMulticompartmental modeling analysis indicated that the median fractional catabolic rates of apo(a) and apoB-100 within Lp(a) were significantly different at 0.104 and 0.263 pools/day, respectively (P=0.04). The median Lp(a) apo(a) production rate at 0.248nmol/kg·day(-1) was significantly lower than that of Lp(a) apoB-100 at 0.514nmol/kg·day(-1) (P=0.03).ConclusionOur data indicate that apo(a) has a plasma residence time (11days) that is more than twice as long as that of apoB-100 (4days) within Lp(a), supporting the concept that apo(a) and apoB-100 within plasma Lp(a) are not catabolized from the bloodstream as a unit in humans in the fed state.

Secondary salinization of freshwater ecosystems is of increasing global concern. One of the main causes are the effluents of the potash mining industry containing high concentrations of major ions (Cl−, Na+, Mg2+, K+). In Germany, the ongoing discharge of effluents into the River Werra led to a strong impoverishment of the biodiversity and abundance of local species. Young cohorts of many freshwater fish are completely absent suggesting reproductive failure under these conditions. Therefore, the aim of the study was to experimentally investigate the effects of high concentrations and imbalances of ions that are prevalent in potash mining effluents on reproductive traits of native freshwater teleosts. Sperm motility parameters of the common roach, Rutilus rutilus, and European perch, Perca fluviatilis, were assessed as well as fertilization rate, egg size, hatching, malformations and mortality of embryonic and larval stages of roach. Concentrations of the permitted thresholds (HT) and future thresholds (LT) as well as three ion solutions containing high Mg2+ (Mg), high K+ (K) and both in combination (Mg + K) were tested. Curvilinear velocity and linearity of perch spermatozoa were elevated with potentially adverse effects on fertilization success. Sperm motility parameters and fertilization rate of roach were not affected. However, egg sizes of roach were increased in all groups due to the osmotic action of ions and in LT, premature hatch was observed. Furthermore, all groups comprised a higher number of malformations including pericardial edema and spine curvatures and group HT exhibited a higher mortality rate compared to control. The results clearly demonstrated that particularly the sum of high concentrations of ions, as prevalent in HT and LT, rather than individual ion species exerts detrimental effects on early development of roach potentially increasing overall mortality under natural conditions. These results emphasize that currently permitted and future thresholds are exceeding tolerated ion concentrations.

Hidradenitis suppurativa (HS) is a chronic, recurring inflammatory dermatosis characterized by abscesses, deep-seated nodules, sinus tracts, and fibrosis in skin lesions around hair follicles of the axillary, inguinal, and anogenital regions. Whereas the exact pathogenesis remains poorly defined, clear evidence suggests that HS is a multifactorial inflammatory disease characterized by innate and adaptive immune components. Bioactive lipids are important regulators of cutaneous homeostasis, inflammation, and resolution of inflammation. Alterations in the lipid mediator profile can lead to malfunction and cutaneous inflammation. We used targeted lipidomics to analyze selected omega-3 and omega-6 polyunsaturated fatty acids in skin of patients with HS and of healthy volunteers. Lesional HS skin displayed enrichment of 5-lipoxygenase (LO)‒derived metabolites, especially leukotriene B4. In addition, 15-LO‒derived metabolites were underrepresented in HS lesions. Changes in the lipid mediator profile were accompanied by transcriptomic dysregulation of the 5-LO and 15-LO pathways. Hyperactivation of the 5-LO pathway in lesional macrophages identified these cells as potential sources of leukotriene B4, which may cause neutrophil influx and activation. Furthermore, leukotriene B4-induced mediators and pathways were elevated in HS lesions, suggesting a contribution of this proinflammatory lipid meditator to the pathophysiology of HS.