Season and prey identity mediate the effect of predators on parasites in rodents: a test of the healthy herds hypothesis.

The healthy herds hypothesis (HHH) suggests that predators decrease parasitism in their prey. Repeated tests of this hypothesis across a range of taxa and ecosystems have revealed significant variation in the effect of predators on parasites in prey. Differences in the response to predators (1) between prey taxa, (2) between seasons, and (3) before and after catastrophic disturbance are common in natural systems, but typically ignored in empirical tests of the HHH. We used a predator exclusion experiment to measure the effect of these heterogeneities on the tri-trophic interaction among predators, parasites and prey. We experimentally excluded mammalian predators from the habitats of hispid cotton rats (Sigmodon hispidus) and cotton mice (Peromyscus gossypinus) and measured the effect of exclusion on gastrointestinal parasites in these rodents. Our experiment spanned multiple seasons and before and after a prescribed burn. We found that the exclusion of the same predators had opposite effects on the parasites of small mammal prey species. Additionally, we found that the effect of mammal exclusion on parasitism differed before versus after fire disturbance. Finally, we saw that the effect of predator exclusion was highly dependent on prey capture season. Significant effects of exclusion emerged primarily in the fall and winter months. The presence of so many different effects in one relatively simple system suggests that predator effects on parasites in prey are highly context dependent.

The effects of CenteringPregnancy on maternal and infant health outcomes: a moderation analysis.

BACKGROUND: CenteringPregnancy (CP) has been expected to produce beneficial outcomes for women and their infants. However, previous studies paid little attention to testing variations in CP's effects across women from different demographic groups. This study aimed to test how multiple demographic factors (obesity, race, ethnicity, marital status and socioeconomic status) moderate CP's effects on health outcomes. METHODS: This study employed a quasi-experimental design. De-identified hospital birth data were collected from 216 CP participants and 1159 non-CP participants. We estimated the average treatment effect of CP on outcome variables as a baseline. Then we estimated the average marginal effect of CP by adding each of the moderating variables in regression adjustment models. RESULTS: CP produced salutary effects among those who were obese or overweight and unmarried as well as women with lower socioeconomic status. These salutary effects were also strengthened as maternal age increased. However, CP was ineffective for Hispanic/Latinx women. CONCLUSIONS: CP produced more beneficial health outcomes for high-risk women such as obese, unmarried women and those with lower socioeconomic status. These are meaningful findings from a public health perspective.

Comparative bone healing with induced membrane technique (IMT) versus empty defects in septic and aseptic conditions in a novel rabbit humerus model.

BACKGROUND: Long bone defects resulting from primary trauma or secondary to debridement of fracture-related infection (FRI) remain a major clinical challenge. One approach often used is the induced membrane technique (IMT). The effectiveness of the IMT in infected versus non-infected settings remains to be definitively established. In this study we present a new rabbit humerus model and compare the IMT approach between animals with prior infection and non-infected equivalents. METHODS: A 5 mm defect was created in the humerus of New Zealand White rabbits (n = 53) and fixed with a 2.5 mm stainless steel plate. In the non-infected groups, the defect was either left empty (n = 6) or treated using the IMT procedure (PMMA spacer for 3 weeks, n = 6). Additionally, both approaches were applied in animals that were inoculated with Staphylococcus aureus 4 weeks prior to defect creation (n = 5 and n = 6, respectively). At the first and second revision surgeries, infected and necrotic tissues were debrided and processed for bacteriological quantification. In the IMT groups, the PMMA spacer was removed 3 weeks post implantation and replaced with a beta-tricalcium phosphate scaffold and bone healing observed for a further 10 weeks. Infected groups also received systemic antibiotic therapy. The differences in bone healing between the groups were evaluated radiographically using a modification of the radiographic union score for tibial fractures (RUST) and by semiquantitative histopathology on Giemsa-Eosin-stained sections. RESULTS: The presence of S. aureus infection at revision surgery was required for inclusion to the second stage. At the second revision surgery all collected samples were culture negative confirming successful treatment. In the empty defect group, bone healing was increased in the previously infected animals compared with non-infected controls as revealed by radiography with significantly higher RUST values at 6 weeks (p = 0.0281) and at the end of the study (p = 0.0411) and by histopathology with increased cortical bridging (80% and 100% in cis and trans cortical bridging in infected animals compared to 17% and 67% in the non-infected animals). With the IMT approach, both infected and non-infected animals had positive healing assessments. CONCLUSION: We successfully developed an in vivo model of bone defect healing with IMT with and without infection. Bone defects can heal after an infection with even better outcomes compared to the non-infected setting, although in both cases, the IMT achieved better healing.

In Vitro Testing and Clinical Handling of a Novel Implant Positioning Technology for Proximal Humeral Plating.

BACKGROUND AND OBJECTIVES: Fractures of the proximal humerus are common, particularly in elderly populations. Anatomical locking plates target stabilization with a multitude of screws spanning into the humeral head. Sound implant placement and screw length determination are key for a successful clinical outcome but are difficult to obtain from planar X-rays. A novel implant positioning technology for proximal humerus plating (Xin1) outputs screw lengths suggestions and plate position based on hole projections in conventional X-ray images. This study investigated the performance of a prototype Xin1 system in a postmortem (in vitro) experiment as well as in a clinical handling test. MATERIALS AND METHODS: For in vitro testing, twelve shoulders from six anatomical specimens were randomized into two groups to compare the Xin1 technique to the conventional operation in terms of surgical precision, procedure time and X-ray exposure. For the clinical trial, 11 patients undergoing plating of the proximal humerus were included. The aim was to investigate clinical handling of the Xin1 marker clip and to retrospectively evaluate the system performance in a real-life fracture situation. Image pairs before and after insertion of the proximal screws were retrospectively processed to investigate the influence of potential bone fragment shifts on the system output. RESULTS: In the postmortem experiment, the use of the system significantly improved the surgical precision (52% error reduction), procedure time (38% shorter) and radiation exposure (64% less X-rays). Clinical handling demonstrated seamless embedding of the marker clip into existing clinical workflows without adverse events reported. Retrospective X-ray analysis on six eligible patients revealed differences in the calculated screw lengths of ≤2 mm before and after screw insertion for five patients. In one patient, the screw lengths differed up to 8 mm, which might indicate displacement of the head fragment. CONCLUSIONS: Results suggest a strong potential of the Xin1 assistance technology to enhance the surgical procedure and patient outcomes in the rising incidence of osteoporotic humeral fractures. Robust performance in a real-life fracture situation was observed. In-depth validation of the system is, however, needed before placing it into clinical practice.

Do predators keep prey healthy or make them sicker? A meta-analysis.

Ecological theory suggests that predators can either keep prey populations healthy by reducing parasite burdens or alternatively, increase parasitism in prey. To quantify the overall magnitude and direction of the effect of predation on parasitism in prey observed in practice, we conducted a meta-analysis of 47 empirical studies. We also examined how study attributes, including parasite type and life cycle, habitat type, study design, and whether predators were able to directly consume prey contributed to variation in the predator-prey-parasite interaction. We found that the overall effect of predation on parasitism differed between parasites and parasitoids and that whether consumptive effects were present, and whether a predator was a non-host spreader of parasites, were the most important traits predicting the parasite response. Our results suggest that the mechanistic basis of predator-prey interactions strongly influences the effects of predators on parasites and that these effects, although context dependent, are predictable.

Process, resource and success factors associated with chimeric antigen receptor T-cell therapy for multiple myeloma.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy represents a new frontier in multiple myeloma. It is important to understand critical success factors (CSFs) that may optimize its use in this therapeutic area. Methods: We estimated the CAR-T process using time-driven activity-based costing. Information was obtained through interviews at four US oncology centers and with payer representatives, and through publicly available data. Results: The CAR-T process comprises 13 steps which take 177 days; it was estimated to include 46 professionals and ten care settings. CSFs included proactive collaboration, streamlined reimbursement and CAR-T administration in alternative settings when possible. Implementing CSFs may reduce episode time and costs by 14.4 and 13.2%, respectively. Conclusion: Our research provides a blueprint for improving efficiencies in CAR-T therapy, thereby increasing its sustainability for multiple myeloma.

Patients with multiple myeloma can now be treated with chimeric antigen receptor T-cell (CAR-T) therapy. We studied how CAR-T therapy is used for multiple myeloma. We also studied things that could help make this therapy easier for doctors to use. The CAR-T process takes 13 steps and 177 days. It begins with the choice to use the therapy and ends about 100 days after it is used. The process uses 46 different healthcare professionals and ten different locations. We found several possible changes that can improve this process. Of these changes, three stand out. First, improved teamwork between members of the care team can help them prepare for and resolve possible problems. Second, reducing insurance red tape will make it easier to provide CAR-T therapy to patients. Third, allowing use of CAR-T therapy in places other than hospitals can help more patients receive this therapy. If applied, these three things may lower the time needed to treat patients by 14.4% and may reduce costs by 13.2%.

Continuous Implant Load Monitoring to Assess Bone Healing Status-Evidence from Animal Testing.

Background and Objectives: Fracture healing is currently assessed through qualitative evaluation of radiographic images, which is highly subjective in nature. Radiographs can only provide snapshots in time, which are limited due to logistics and radiation exposure. We recently proposed assessing the bone healing status through continuous monitoring of the implant load, utilizing an implanted sensor system, the Fracture Monitor. The device telemetrically transmits statistically derived implant parameters via the patient's mobile phone to assist physicians in diagnostics and treatment decision-making. This preclinical study aims to systematically investigate the device safety and performance in an animal setting. Materials and Methods: Mid-shaft tibial osteotomies of different sizes (0.6-30 mm) were created in eleven Swiss mountain sheep. The bones were stabilized with either a conventional Titanium or stainless-steel locking plate equipped with a Fracture Monitor. Data were continuously collected over the device's lifetime. Conventional radiographs and clinical CT scans were taken longitudinally over the study period. The radiographs were systematically scored and CTs were evaluated for normalized bone volume in the defect. The animals were euthanized after 9 months. The sensor output was correlated with the radiologic parameters. Tissue samples from the device location were histologically examined. Results: The sensors functioned autonomously for 6.5-8.4 months until energy depletion. No macroscopic or microscopic adverse effects from device implantation were observed. The relative implant loads at 4 and 8 weeks post-operation correlated significantly with the radiographic scores and with the normalized bone volume metric. Conclusions: Continuous implant load monitoring appears as a relevant approach to support and objectify fracture healing assessments and carries a strong potential to enable patient-tailored rehabilitation in the future.

Continuous Rod Load Monitoring to Assess Spinal Fusion Status-Pilot In Vivo Data in Sheep.

Background and Objectives: Spinal fusion is an effective and widely accepted intervention. However, complications such as non-unions and hardware failures are frequently observed. Radiologic imaging and physical examination are still the gold standards in the assessment of spinal fusion, despite multiple limitations including radiation exposure and subjective image interpretation. Furthermore, current diagnostic methods only allow fusion assessment at certain time points and require the patient's presence at the hospital or medical practice. A recently introduced implantable sensor system for continuous and wireless implant load monitoring in trauma applications carries the potential to overcome these drawbacks, but transferability of the principle to the spine has not been demonstrated yet. Materials and Methods: The existing trauma sensor was modified for attachment to a standard pedicle-screw-rod system. Two lumbar segments (L2 to L4) of one Swiss white alpine sheep were asymmetrically instrumented. After facetectomy, three sensors were attached to the rods between each screw pair and activated for measurement. The sheep was euthanized 16 weeks postoperatively. After radiological assessment the spine was explanted and loaded in flexion-extension to determine the range of motion of the spinal segments. Sensor data were compared with mechanical test results and radiologic findings. Results: The sensors measured physiological rod loading autonomously over the observation period and delivered the data daily to bonded smartphones. At euthanasia the relative rod load dropped to 67% of the respective maximum value for the L23 segment and to 30% for the L34 segment. In agreement, the total range of motion of both operated segments was lower compared to an intact reference segment (L23: 0.57°; L34: 0.49°; intact L45: 4.17°). Radiologic assessment revealed fusion mass in the facet joint gaps and bilateral bridging bone around the joints at both operated segments. Conclusions: Observations of this single-case study confirm the basic ability of continuous rod load measurement to resolve the spinal fusion process as indicated by a declining rod load with progressing bone fusion. A strong clinical potential of such technology is eminent, but further data must be collected for final proof of principle.

Non-self mutation: double-stranded RNA elicits antiviral pathogenic response in a Drosophila model of expanded CAG repeat neurodegenerative diseases.

Inflammation is activated prior to symptoms in neurodegenerative diseases, providing a plausible pathogenic mechanism. Indeed, genetic and pharmacological ablation studies in animal models of several neurodegenerative diseases demonstrate that inflammation is required for pathology. However, while there is growing evidence that inflammation-mediated pathology may be the common mechanism underlying neurodegenerative diseases, including those due to dominantly inherited expanded repeats, the proximal causal agent is unknown. Expanded CAG.CUG repeat double-stranded RNA causes inflammation-mediated pathology when expressed in Drosophila. Repeat dsRNA is recognized by Dicer-2 as a foreign or 'non-self' molecule triggering both antiviral RNA and RNAi pathways. Neither of the RNAi pathway cofactors R2D2 nor loquacious are necessary, indicating antiviral RNA activation. RNA modification enables avoidance of recognition as 'non-self' by the innate inflammatory surveillance system. Human ADAR1 edits RNA conferring 'self' status and when co-expressed with expanded CAG.CUG dsRNA in Drosophila the pathology is lost. Cricket Paralysis Virus protein CrPV-1A is a known antagonist of Argonaute-2 in Drosophila antiviral defense. CrPV-1A co-expression also rescues pathogenesis, confirming anti-viral-RNA response. Repeat expansion mutation therefore confers 'non-self' recognition of endogenous RNA, thereby providing a proximal, autoinflammatory trigger for expanded repeat neurodegenerative diseases.

A Hyaluronic Acid Hydrogel Loaded with Gentamicin and Vancomycin Successfully Eradicates Chronic Methicillin-Resistant Staphylococcus aureus Orthopedic Infection in a Sheep Model.

Implantable orthopedic devices have had an enormously positive impact on human health; however, despite best practice, patients are prone to developing orthopedic device-related infections (ODRI) that have high treatment failure rates. One barrier to the development of improved treatment options is the lack of an animal model that may serve as a robust preclinical assessment of efficacy. We present a clinically relevant large animal model of chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI that persists despite current clinical practice in medical and surgical treatment at rates equivalent to clinical observations. Furthermore, we showed that an injectable, thermoresponsive, hyaluronic acid-based hydrogel loaded with gentamicin and vancomycin outperforms current clinical practice treatment in this model, eliminating bacteria from all animals. These results confirm that local antibiotic delivery with an injectable hydrogel can dramatically increase treatment success rates beyond current clinical practice, with efficacy proven in a robust animal model.

Current Concepts of Osteomyelitis: From Pathologic Mechanisms to Advanced Research Methods.

Osteomyelitis is an inflammation of the bone and bone marrow that is most commonly caused by a Staphylococcus aureus infection. Much of our understanding of the underlying pathophysiology of osteomyelitis, from the perspective of both host and pathogen, has been revised in recent years, with notable discoveries including the role played by osteocytes in the recruitment of immune cells, the invasion and persistence of S. aureus in submicron channels of cortical bone, and the diagnostic role of polymorphonuclear cells in implant-associated osteomyelitis. Advanced in vitro cell culture models, such as ex vivo culture models or organoids, have also been developed over the past decade, and have become widespread in many fields, including infectious diseases. These models better mimic the in vivo environment, allow the use of human cells, and can reduce our reliance on animals in osteomyelitis research. In this review, we provide an overview of the main pathologic concepts in osteomyelitis, with a focus on the new discoveries in recent years. Furthermore, we outline the value of modern in vitro cell culture techniques, with a focus on their current application to infectious diseases and osteomyelitis in particular.

Cortical parameters predict bone strength at the tibial diaphysis, but are underestimated by HR-pQCT and µCT compared to histomorphometry.

Cortical bone and its microstructure are crucial for bone strength, especially at the long bone diaphysis. However, it is still not well-defined how imaging procedures can be used as predictive tools for mechanical bone properties. This study evaluated the capability of several high-resolution imaging techniques to capture cortical bone morphology and assessed the correlation with the bone's mechanical properties. The microstructural properties (cortical thickness [Ct.Th], porosity [Ct.Po], area [Ct.Ar]) of 11 female tibial diaphysis (40-90 years) were evaluated by dual-energy X-ray absorptiometry (DXA), high-resolution peripheral-quantitative-computed-tomography (HR-pQCT), micro-CT (µCT) and histomorphometry. Stiffness and maximal torque to failure were determined by mechanical testing. T-Scores determined by DXA ranged from 0.6 to -5.6 and a lower T-Score was associated with a decrease in Ct.Th (p ≤ 0.001) while the Ct.Po (p ≤ 0.007) increased, and this relationship was independent of the imaging method. With decreasing T-Score, histology showed an increase in Ct.Po from the endosteal to the periosteal side (p = 0.001) and an exponential increase in the ratio of osteons at rest to those after remodelling. However, compared to histomorphometry, HR-pQCT and µCT underestimated Ct.Po and Ct.Th. A lower T-Score was also associated with significantly reduced stiffness (p = 0.031) and maximal torque (p = 0.006). Improving the accuracy of Ct.Po and Ct.Th did not improve prediction of the mechanical properties, which was most closely related to geometry (Ct.Ar). The ex-vivo evaluation of mechanical properties correlated with all imaging modalities, with Ct.Th and Ct.Po highly correlated with the T-Score of the tibial diaphysis. Cortical microstructural changes were underestimated with the lower resolution of HR-pQCT and µCT compared to the histological 'gold standard'. The increased accuracy did not result in an improved prediction for local bone strength in this study, which however might be related to the limited number of specimens and thus needs to be evaluated in a larger collective.

Scabies: Diagnostic and Therapeutic Update.

BACKGROUND: Scabies is globally ubiquitous and is a significant health issue for institutions, the economically disenfranchised, resource-poor areas, and for those with weakened immune systems. Topicals are usually effective, but are cumbersome and expensive to use in large populations and for those nonadherent to topicals. Oral ivermectin became available in Canada for the off-label treatment of scabies in the fall 2018. OBJECTIVES: To review the diagnosis and management of scabies. Dose schedules and concomitant management measures are outlined for scabies simplex and for crusted scabies. Ivermectin use is outlined. METHODS: Medline, colleague discussions, practice review, and experience from managing scabies in institutions. RESULTS: Oral ivermectin is safe, easier to use, cheaper, more effective, and more economical than topicals in widespread institutional scabies, for those nonadherent to topicals, and in crusted scabies. CONCLUSIONS: Oral ivermectin is the treatment of choice in large populations, the nonadherent, and for crusted scabies. Oral ivermectin is produced by Merck Canada as Stromectol 3 mg. The treatment dose for noncrusted scabies is 200 µg/kg, taken in a single dose with food. For example, 15 mg (5 tablets) for a 70 kg person. Retreat in 10-14 days to enhance effectiveness, and perhaps to reduce scabicide resistance.

Alpha-Gal Allergy as a Cause of Intestinal Symptoms in a Gastroenterology Community Practice.

OBJECTIVES: Immunoglobulin E (IgE) to galactose-α-1,3-galactose (alpha-gal) is a recently appreciated cause of allergic reactions to mammalian meat and dairy. In eastern North America Lone Star tick bites are the dominant mode of sensitization. Classically the alpha-gal syndrome manifests with urticaria, gastrointestinal symptoms, and/or anaphylaxis, but increasingly there are reports of isolated gastrointestinal symptoms without other common allergic manifestations. The objective of this retrospective study was to determine the frequency of IgE to alpha-gal in patients presenting with unexplained gastrointestinal symptoms to a community gastroenterology practice, and to evaluate the symptom response to the removal of mammalian products from the diet in alpha-gal-positive individuals. METHODS: An electronic medical record database was used to identify patients with alpha-gal IgE laboratory testing performed within the past 4 years. These charts were reviewed for alpha-gal test results, abdominal pain, diarrhea, nausea and vomiting, hives, bronchospasm, diagnosis of irritable bowel syndrome, postprandial exacerbation of symptoms, meat exacerbation of symptoms, patient recall of tick bite, other simultaneous gastrointestinal tract diagnoses, and clinical improvement with mammalian food product avoidance. RESULTS: A total of 1112 adult patients underwent alpha-gal IgE testing and 359 (32.3%) were positive. Gastrointestinal symptoms were similar in those positive and negative for alpha-gal seroreactivity. Of the 359 alpha-gal-positive patients, 122 had follow-up data available and 82.0% of these improved on a diet free of mammalian products. Few patients reported hives (3.9%) or bronchospasm (2.2%). Serum alpha-gal IgE titers ranged from 0.1 to >100 kU/L, with an average of 3.43 kU/L and a median of 0.94 kU/L. CONCLUSIONS: Clinicians practicing in the region of the Lone Star tick habitat need to be aware that patients with IgE to alpha-gal can manifest with isolated abdominal pain and diarrhea, and these patients respond well to dietary exclusion of mammalian products.

Thermal Imaging Metrology Using High Dynamic Range Near-Infrared Photovoltaic-Mode Camera.

The measurement of a wide temperature range in a scene requires hardware capable of high dynamic range imaging. We describe a novel near-infrared thermal imaging system operating at a wavelength of 940 nm based on a commercial photovoltaic mode high dynamic range camera and analyse its measurement uncertainty. The system is capable of measuring over an unprecedently wide temperature range; however, this comes at the cost of a reduced temperature resolution and increased uncertainty compared to a conventional CMOS camera operating in photodetective mode. Despite this, the photovoltaic mode thermal camera has an acceptable level of uncertainty for most thermal imaging applications with an NETD of 4-12 °C and a combined measurement uncertainty of approximately 1% K if a low pixel clock is used. We discuss the various sources of uncertainty and how they might be minimised to further improve the performance of the thermal camera. The thermal camera is a good choice for imaging low frame rate applications that have a wide inter-scene temperature range.

Screening of two freshwater green microalgae in pulp and paper mill wastewater effluents in Nova Scotia, Canada.

In recent years, the use of microalgae as feedstock for many marketable products, such as animal/aqua feeds, bioplastics and fertilizers, has gained renewed interest due to their fast growth potential coupled with relatively high lipid, carbohydrate and nutrient content. An algal biorefinery at an industrial site has the potential to sustainably and profitably convert carbon dioxide emissions into microalgal biomass and concomitantly reduce nitrogen and phosphorus from wastewaters. Industrial wastewaters are a potential alternative to traditional media used for large-scale microalgal cultivation. Pulp and paper mills are major consumers of water resources and discharge a huge amount of water to nearby lakes or rivers. This study investigated whether pulp and paper mill waste water is suitable for microalgal cultivation with the aim of achieving significant biomass production. Six different process waters from one Canadian pulp and paper mill were tested with two freshwater green microalgae. All of these waters were unable to support growth of microalgae due to inadequate nutrient concentrations, colour, turbidity and possible toxicity issues.

Neurodegenerative diseases have genetic hallmarks of autoinflammatory disease.

The notion that one common pathogenic pathway could account for the various clinically distinguishable, typically late-onset neurodegenerative diseases might appear unlikely given the plethora of diverse primary causes of neurodegeneration. On the contrary, an autoinflammatory pathogenic mechanism allows diverse genetic and environmental factors to converge into a common chain of causality. Inflammation has long been known to correlate with neurodegeneration. Until recently this relationship was seen as one of consequence rather than cause-with inflammatory cells and events acting to 'clean up the mess' after neurological injury. This explanation is demonstrably inadequate and it is now clear that inflammation is at the very least, rate-limiting for neurodegeneration (and more likely, a principal underlying cause in most if not all neurodegenerative diseases), protective in its initial acute phase, but pernicious in its latter chronic phase.

A New Surface Landmark for Thumb Digital Nerve Bifurcation: A Cadaveric Study.

PURPOSE: The radial and ulnar thumb digital nerves are critical for tactile sensation and dexterity in the hand. This cadaveric study sought to validate a surface landmark for the bifurcation of the thumb radial digital nerve (RDN) and ulnar digital nerve (UDN). METHODS: We used 24 fresh-frozen cadaveric specimens for dissections. With the thumb placed in the plane of the palm and fully radially abducted, the index finger metacarpophalangeal joint was flexed to 90°. Then, while keeping the distal interphalangeal joint straight, the proximal interphalangeal joint was flexed until the fingertip contacted the thenar eminence to identify the point of bifurcation. We made a U-shaped incision and identified the bifurcation of the thumb RDN and UDN. The point of bifurcation was measured from the ulnar- and proximal-most aspects of the incision. RESULTS: The bifurcation of the thumb RDN and UDN was consistently identified within the U in 22 of 24 specimens (92%). In 16 specimens, the index RDN was also identified either trifurcating with the thumb RDN and UDN or branching from a common digital nerve of index RDN and thumb UDN. Most bifurcation points were found directly along the ulnar and proximal edge of the incision. Two specimens contained a bifurcation point 2 mm ulnar to the ulnar limb of the U. CONCLUSIONS: The bifurcation U is a consistent landmark for the thumb RDN and UDN point of bifurcation. The variable branching patterns in this region confirms the importance of thorough clinical examination with penetrating injuries to the thenar eminence. CLINICAL RELEVANCE: This surface anatomic landmark for the thumb RDN and UDN bifurcation may aid in preventing iatrogenic injuries during elective procedures and identifying at-risk structures during penetrating injuries to the palm.

3D statistical model of the pelvic ring - a CT-based statistical evaluation of anatomical variation.

The pelvic ring is a highly complex construct with a central role for human stability and mobility. The observable interindividual differences in skeletal anatomy are caused by anatomical variation in the innominate bones as well as the sacrum, further to differences in the spatial arrangement of these bones to each other. The aim of this study was to generate a 3D statistical model of the entire pelvic ring in order to analyse the observed interindividual differences and anatomical variation. A series of 50 anonymized pelvic CT scans of uninjured Japanese adults [30 males, 20 females, average age of 74.9 years, standard deviation (SD) 16.9 years] were processed and analysed, resulting in a 3D statistical overall mean model and separate male and female mean models. Principal component analysis (PCA) of the overall statistical model predominantly showed size variation (20.39%) followed by shape variation (14.13%), and a variation of the spatial arrangement of the sacrum to the innominate bones in different anatomical peculiarities (11.39 and 8.85%). In addition, selected internal and external pelvic parameters were manually measured with the objective of further evaluating and quantifying the observed interindividual as well as the known sex-specific differences. A separate statistical model of the grey value distribution based on the given Hounsfield unit (HU) values was calculated for assessing bone mass distribution, thus an indication of bone quality utilizing grey values as a quantitative description of radiodensity was obtained. A consistent pattern of grey value distribution was shown, with the highest grey values observed between the sacro-iliac joint and the acetabulum along the pelvic brim. Low values were present in the sacral ala, in the area of the iliac fossa as well as in the pubic rami next to the symphysis. The present model allows a differentiated analysis of the observed interindividual variation of the pelvic ring and an evaluation of the grey value distribution therein. Besides providing a better understanding of anatomical variation, this model could be also used as a helpful tool for educational purposes, preoperative planning and implant design.

Nitric Oxide Mediates Nitrite-Sensing and Acclimation and Triggers a Remodeling of Lipids.

Nitric oxide (NO) is an intermediate of the nitrogen cycle, an industrial pollutant, and a marker of climate change. NO also acts as a gaseous transmitter in a variety of biological processes. The impact of environmental NO needs to be addressed. In diatoms, a dominant phylum in phytoplankton, NO was reported to mediate programmed cell death in response to diatom-derived polyunsaturated aldehydes. Here, using the Phaeodactylum Pt1 strain, 2E,4E-decadienal supplied in the micromolar concentration range led to a nonspecific cell toxicity. We reexamined NO biosynthesis and response in Phaeodactylum NO inhibits cell growth and triggers triacylglycerol (TAG) accumulation. Feeding experiments indicate that NO is not produced from Arg but via conversion of nitrite by the nitrate reductase. Genome-wide transcriptional analysis shows that NO up-regulates the expression of the plastid nitrite reductase and genes involved in the subsequent incorporation of ammonium into amino acids, via both Gln synthesis and Orn-urea pathway. The phosphoenolpyruvate dehydrogenase complex is also up-regulated, leading to the production of acetyl-CoA, which can feed TAG accumulation upon exposure to NO. Transcriptional reprogramming leading to higher TAG content is balanced with a decrease of monogalactosyldiacylglycerol (MGDG) in the plastid via posttranslational inhibition of MGDG synthase enzymatic activity by NO. Intracellular and transient NO emission acts therefore at the basis of a nitrite-sensing and acclimating system, whereas a long exposure to NO can additionally induce a redirection of carbon to neutral lipids and a stress response.