The Impact of Epidural Analgesia on Immobility and extended Hospital Stay After Periacetabular Osteotomy.

AIMS: Early mobilisation after periacetabular osteotomy (PAO) represents an important goal after surgery. The purpose of this study was to determine whether the use of epidural aznalgesia (EA) is associated with prolonged immobility and an increased length of stay (LOS) after PAO surgery. METHODS: From January 2022 to July 2023, the study included a cohort of 150 PAO procedures all performed by the same surgeon (SSA). Patients were categorized into two distinct groups: those who received epidural analgesia (EA) (79 PAOs) and those who did not receive EA (71 PAOs). "Ready for discharge" was defined as the ability to ascend and descend a standardized flight of stairs independently. Multivariable linear regression was used to identify additional factors influencing LOS after PAO. RESULTS: Patients in the EA group were ready for discharge 5.95 ± 2.09 days after surgery which was significantly longer than in the No EA group´s average of 4.18 days ± 2.5, (p < 0.001). While the reduction in the number of patients experiencing pulmonary embolism in the No EA group did not reach statistical significance, it still demonstrated a relevant decrease from two patients within the EA group (2.53%) to 0 (0%) in the No EA group. The active engagement of the surgeon in mobilising patients led to a substantial reduction in LOS, decreasing it from 5.81 ± 2.18 days to 2.2 ± 0.77 days (p < 0.001). Multivariable analysis revealed five independent factors influencing the LOS following PAO which included absence of EA, surgeon-led mobilisation within 24 h after surgery, postoperative hemoglobin levels, BMI, and prior experience with PAO surgery on the contralateral side. CONCLUSIONS: Opting against the use of EA in patients undergoing PAO is advisable, as it will result in extended postoperative immobility and the associated risks. Additionally, the active participation of the surgeon in the mobilisation process is strongly recommended.

Unveiling the learning curve of periacetabular osteotomy.

Aims: Periacetabular osteotomy (PAO) is widely recognized as a demanding surgical procedure for acetabular reorientation. Reports about the learning curve have primarily focused on complication rates during the initial learning phase. Therefore, our aim was to assess the PAO learning curve from an analytical perspective by determining the number of PAOs required for the duration of surgery to plateau and the accuracy to improve. Methods: The study included 118 consecutive PAOs in 106 patients. Of these, 28 were male (23.7%) and 90 were female (76.3%). The primary endpoint was surgical time. Secondary outcome measures included radiological parameters. Cumulative summation analysis was used to determine changes in surgical duration. A multivariate linear regression model was used to identify independent factors influencing surgical time. Results: The learning curve in this series was 26 PAOs in a period of six months. After 26 PAO procedures, a significant drop in surgical time was observed and a plateau was also achieved. The mean duration of surgery during the learning curve was 103.8 minutes (SD 33.2), and 69.7 minutes (SD 18.6) thereafter (p < 0.001). Radiological correction of acetabular retroversion showed a significant improvement after having performed a total of 93 PAOs, including anteverting PAOs on 35 hips with a retroverted acetabular morphology (p = 0.005). Several factors were identified as independent variables influencing duration of surgery, including patient weight (ß = 0.5 (95% confidence interval (CI) 0.2 to 0.7); p < 0.001), learning curve procedure phase of 26 procedures (ß = 34.0 (95% CI 24.3 to 43.8); p < 0.001), and the degree of lateral correction expressed as the change in the lateral centre-edge angle (ß = 0.7 (95% CI 0.001 to 1.3); p = 0.048). Conclusion: The learning curve for PAO surgery requires extensive surgical training at a high-volume centre, with a minimum of 50 PAOs per surgeon per year. This study defined a cut-off value of 26 PAO procedures, after which a significant drop in surgical duration occurred. Furthermore, it was observed that a retroverted morphology of the acetabulum required a greater number of procedures to acquire proficiency in consistently eliminating the crossover sign. These findings are relevant for fellows and fellowship programme directors in establishing the extent of training required to impart competence in PAO.

Progeny counter mechanism in malaria parasites is linked to extracellular resources.

Malaria is caused by the rapid proliferation of Plasmodium parasites in patients and disease severity correlates with the number of infected red blood cells in circulation. Parasite multiplication within red blood cells is called schizogony and occurs through an atypical multinucleated cell division mode. The mechanisms regulating the number of daughter cells produced by a single progenitor are poorly understood. We investigated underlying regulatory principles by quantifying nuclear multiplication dynamics in Plasmodium falciparum and knowlesi using super-resolution time-lapse microscopy. This confirmed that the number of daughter cells was consistent with a model in which a counter mechanism regulates multiplication yet incompatible with a timer mechanism. P. falciparum cell volume at the start of nuclear division correlated with the final number of daughter cells. As schizogony progressed, the nucleocytoplasmic volume ratio, which has been found to be constant in all eukaryotes characterized so far, increased significantly, possibly to accommodate the exponentially multiplying nuclei. Depleting nutrients by dilution of culture medium caused parasites to produce fewer merozoites and reduced proliferation but did not affect cell volume or total nuclear volume at the end of schizogony. Our findings suggest that the counter mechanism implicated in malaria parasite proliferation integrates extracellular resource status to modify progeny number during blood stage infection.

Development of early complications after treatment of trochanteric fractures with an intramedullary sliding hip screw in a geriatric population.

PURPOSE: Although trochanteric fractures (TF) are a frequent event in the geriatric population, studies reporting on complication rates associated with surgical treatment are sparse. Thus, this study investigated the relevance of fracture-, implant-, and surgery-associated complications in TF. Furthermore, the role of possible risk factors for the before mentioned complications was investigated. METHODS: A consecutive series of patients with TF treated by intramedullary nailing with a sliding screw device was evaluated. Data were sampled retrospectively from the hospital patient information system and anonymized at the source. Demographic data and information regarding fracture pattern, the treatment performed, hospital stay, and evaluation of operative and follow-up radiographs were analyzed. Intraoperative problems (i.e., technical problems with the implant, intraoperative fracture) and postoperative complications were investigated. RESULTS: Postoperative surgical complications were noted in 11.7%. The most frequent surgical problem was a difficult fracture reduction (13%) and intraoperative fracture dislocation (3.6%). The most frequent postoperative complication was intra-hospital mortality (3.6%), delayed/non-union (2.7%), and a cut-out of the lag screw in the femoral head (2.3%). Implant failure (1,4%) was significantly associated with morbid obesity while cut-out (2,3%) correlated with a higher tip-apex distance (TAD). A complex fracture type and a suboptimal screw position significantly increased the cut-out rate to 5% (p = 0.018). CONCLUSION: Complications after TF treatment occur frequently. While patient-associated variables such as morbid obesity cannot be influenced by the surgeon, correct fracture reduction and implant positioning remain to be of highest importance.

Trade-offs between cost and information in cellular prediction.

Living cells can leverage correlations in environmental fluctuations to predict the future environment and mount a response ahead of time. To this end, cells need to encode the past signal into the output of the intracellular network from which the future input is predicted. Yet, storing information is costly while not all features of the past signal are equally informative on the future input signal. Here, we show for two classes of input signals that cellular networks can reach the fundamental bound on the predictive information as set by the information extracted from the past signal: Push-pull networks can reach this information bound for Markovian signals, while networks that take a temporal derivative can reach the bound for predicting the future derivative of non-Markovian signals. However, the bits of past information that are most informative about the future signal are also prohibitively costly. As a result, the optimal system that maximizes the predictive information for a given resource cost is, in general, not at the information bound. Applying our theory to the chemotaxis network of Escherichia coli reveals that its adaptive kernel is optimal for predicting future concentration changes over a broad range of background concentrations, and that the system has been tailored to predicting these changes in shallow gradients.

Unsaturated Long-Chain Fatty Acids Activate Resident Macrophages and Stem Cells in a Human Skeletal Muscle Tissue Model.

Phenotypically heterogeneous populations of tissue-resident macrophages and stem cells play important roles in the regeneration of the skeletal muscle tissue. Previous studies using animal and cell culture models implied a beneficial effect of fatty acid (FA) species on tissue regeneration. Here, we applied a human experimental model using excised muscle tissues from reconstructive surgeries to study the effects of FAs on resident macrophages and stem cells in the natural environment of human skeletal muscle tissue. Muscle tissue samples from 20 donors were included in this study. The expression of 34 cytokines/chemokines was determined, using multiplex protein analysis. The phenotypes of macrophages and stem cells were determined immunohistochemically. The numbers of CD80+ macrophages correlated with the expression levels of IL-1α, IL-1RA, IL-8, IL-17A, and MCP-1, while the PAX7+ and MyoD+ stem cell counts were positively correlated with the expression level of CXCL12α, a recognized chemoattractant for muscle stem cells. Treatment of additional tissue sections with FAs revealed that CD80+ or MARCO+ macrophages- and PAX7+ or MyoD+ stem cells were simultaneously increased by unsaturated long-chain FAs. Taken together, this is the first experimental demonstration of a coordinated activation of macrophages and stem cells in human skeletal muscle tissue.

Effect of Injury Patterns on the Development of Complications and Trauma-Induced Mortality in Patients Suffering Multiple Trauma.

Patients that suffer from severe multiple trauma are highly vulnerable to the development of complications that influence their outcomes. Therefore, this study aimed to evaluate the risk factors that can facilitate an early recognition of adult patients at risk. The inclusion criteria were as follows: admission to a level 1 trauma center, injury severity score (ISS) ≥ 16 (severe injury was defined by an abbreviated injury score (AIS) ≥ 3) and ≥18 years of age. Injury- and patient-associated factors were correlated with the development of four complication clusters (surgery-related, infection, thromboembolic events and organ failure) and three mortality time points (immediate (6 h after admission), early (>6 h-72 h) and late (>72 h) mortality). Statistical analysis was performed using a Chi-square, Mann-Whitney U test, Cox hazard regression analysis and binominal logistic regression analysis. In total, 383 patients with a median ISS of 24 (interquartile range (IQR) 17-27) were included. The overall mortality rate (27.4%) peaked in the early mortality group. Lactate on admission significantly correlated with immediate and early mortality. Late mortality was significantly influenced by severe head injuries in patients with a moderate ISS (ISS 16-24). In patients with a high ISS (≥25), late mortality was influenced by a higher ISS, older age and higher rates of organ failure. Complications were observed in 47.5% of all patients, with infections being seen most often. The development of complications was significantly influenced by severe extremity injuries, the duration of mechanical ventilation and length of ICU stay. Infection remains the predominant posttraumatic complication. While immediate and early mortality is mainly influenced by the severity of the initial trauma, the rates of severe head injuries influence late mortality in moderate trauma severity, while organ failure remains a relevant factor in patients with a high injury severity.

Quantitating CD8+ T cell memory development.

In acute immune responses to infection, memory T cells develop that can spawn recall responses. This process has not been observable directly in vivo. Here we highlight the utility of mathematical inference to derive quantitatively testable models of mammalian CD8+ T cell memory development from complex experimental data. Previous inference studies suggested that precursors of memory T cells arise early during the immune response. Recent work has both validated a crucial prediction of this T cell diversification model and refined the model. While multiple developmental routes to distinct memory subsets might exist, a branch point occurs early in proliferating T cell blasts, from which separate differentiation pathways emerge for slowly dividing precursors of re-expandable memory cells and rapidly dividing effectors.

Fifty percent of patients undergoing periacetabular osteotomy for hip dysplasia showed normal findings upon neonatal ultrasound screening : Symptomatic hip dysplasia in adulthood despite inconspicuous neonatal hip ultrasound.

Developmental dysplasia of the hip (DDH) is characterized by the pathomorphology of inadequate acetabular coverage of the femoral head leading to increased loading of the articular surface and acetabular rim. If left untreated, this ultimately leads to osteoarthritis. Germany introduced a nationwide universal ultrasound screening program for all newborn infants in 1996. Subsequently, the incidence of undiagnosed hip dislocation was significantly reduced. In this consecutive series of patients who underwent periacetabular osteotomy for the treatment of symptomatic dysplasia of the hip between October 2014 and October 2022 data regarding the U3 screening examination were analyzed. The data included whether the examination was performed, whether the findings were positive or negative, whether the patients underwent any form of treatment in the case of a positive finding and whether a control X­ray was performed. This study provides evidence that acetabular undercoverage cannot be ruled out based on a normal finding in ultrasonography screening. Furthermore, the study also shows that residual dysplasia may persist despite attempts of conservative treatment.

Pyrimidine de novo synthesis inhibition selectively blocks effector but not memory T cell development.

Blocking pyrimidine de novo synthesis by inhibiting dihydroorotate dehydrogenase is used to treat autoimmunity and prevent expansion of rapidly dividing cell populations including activated T cells. Here we show memory T cell precursors are resistant to pyrimidine starvation. Although the treatment effectively blocked effector T cells, the number, function and transcriptional profile of memory T cells and their precursors were unaffected. This effect occurred in a narrow time window in the early T cell expansion phase when developing effector, but not memory precursor, T cells are vulnerable to pyrimidine starvation. This vulnerability stems from a higher proliferative rate of early effector T cells as well as lower pyrimidine synthesis capacity when compared with memory precursors. This differential sensitivity is a drug-targetable checkpoint that efficiently diminishes effector T cells without affecting the memory compartment. This cell fate checkpoint might therefore lead to new methods to safely manipulate effector T cell responses.

CycleFlow simultaneously quantifies cell-cycle phase lengths and quiescence in vivo.

Populations of stem, progenitor, or cancer cells show proliferative heterogeneity in vivo, comprising proliferating and quiescent cells. Consistent quantification of the quiescent subpopulation and progression of the proliferating cells through the individual phases of the cell cycle has not been achieved. Here, we describe CycleFlow, a method that robustly infers this comprehensive information from standard pulse-chase experiments with thymidine analogs. Inference is based on a mathematical model of the cell cycle, with realistic waiting time distributions for the G1, S, and G2/M phases and a long-term quiescent G0 state. We validate CycleFlow with an exponentially growing cancer cell line in vitro. Applying it to T cell progenitors in steady state in vivo, we uncover strong proliferative heterogeneity, with a minority of CD4+CD8+ T cell progenitors cycling very rapidly and then entering quiescence. CycleFlow is suitable as a routine method for quantitative cell-cycle analysis.

Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis.

Hematopoietic stem cells (HSCs) produce highly diverse cell lineages. Here, we chart native lineage pathways emanating from HSCs and define their physiological regulation by computationally integrating experimental approaches for fate mapping, mitotic tracking, and single-cell RNA sequencing. We find that lineages begin to split when cells leave the tip HSC population, marked by high Sca-1 and CD201 expression. Downstream, HSCs either retain high Sca-1 expression and the ability to generate lymphocytes, or irreversibly reduce Sca-1 level and enter into erythro-myelopoiesis or thrombopoiesis. Thrombopoiesis is the sum of two pathways that make comparable contributions in steady state, a long route via multipotent progenitors and CD48hi megakaryocyte progenitors (MkPs), and a short route from HSCs to developmentally distinct CD48-/lo MkPs. Enhanced thrombopoietin signaling differentially accelerates the short pathway, enabling a rapid response to increasing demand. In sum, we provide a blueprint for mapping physiological differentiation fluxes from HSCs and decipher two functionally distinct pathways of native thrombopoiesis.

In Vitro Model of Human Skeletal Muscle Tissue for the Study of Resident Macrophages and Stem Cells.

Findings from studies of muscle regeneration can significantly contribute to the treatment of age-related loss of skeletal muscle mass, which may predispose older adults to severe morbidities. We established a human experimental model using excised skeletal muscle tissues from reconstructive surgeries in eight older adults. Muscle samples from each participant were preserved immediately or maintained in agarose medium for the following 5, 9, or 11 days. Immunofluorescence analyses of the structural proteins, actin and desmin, confirmed the integrity of muscle fibers over 11 days of maintenance. Similarly, the numbers of CD80-positive M1 and CD163-positive M2 macrophages were stable over 11 days in vitro. However, the numbers of PAX7-positive satellite cells and MYOD-positive myoblasts changed in opposite ways, suggesting that satellite cells partially differentiated in vitro. Further experiments revealed that stimulation with unsaturated fatty acid C18[2]c (linoleic acid) increased resident M1 macrophages and satellite cells specifically. Thus, the use of human skeletal muscle tissue in vitro provides a direct experimental approach to study the regulation of muscle tissue regeneration by macrophages and stem cells and their responses to therapeutic compounds.

Asynchronous nuclear cycles in multinucleated Plasmodium falciparum facilitate rapid proliferation.

Malaria-causing parasites proliferate within erythrocytes through schizogony, forming multinucleated stages before cellularization. Nuclear multiplication does not follow a strict geometric 2n progression, and each proliferative cycle produces a variable number of progeny. Here, by tracking nuclei and DNA replication, we show that individual nuclei replicate their DNA at different times, despite residing in a shared cytoplasm. Extrapolating from experimental data using mathematical modeling, we provide strong indication that a limiting factor exists, which slows down the nuclear multiplication rate. Consistent with this prediction, our data show that temporally overlapping DNA replication events were significantly slower than partially overlapping or nonoverlapping events. Our findings suggest the existence of evolutionary pressure that selects for asynchronous DNA replication, balancing available resources with rapid pathogen proliferation.

Patient-specific risk factors for adverse outcomes following geriatric proximal femur fractures.

BACKGROUND: Proximal femur fractures (PFFs) occur frequently among geriatric patients due to diverse risk factors, such as a lower bone mineral density and the increased risk of falls. METHODS: In this review, we focus on recent literature of patient-specific risk factors and their impact on common complications and outcome parameters in patients with PFF. RESULTS: Patient- and treatment related factors have a significant impact on outcome and are associated with an increased risk of mortality, impairments in functional rehabilitation and complicative courses. CONCLUSION: Geriatric patients at high risk for complications are nursing home inhabitants suffering from severe osteoporosis, dementia and sarcopenia. The early and ongoing assessment for these individual risk factors is crucial. Strategies including interdisciplinary approaches, addressing comorbidities and facilitating an optimal risk factor evaluation result in a beneficial outcome. The ongoing ambulant assessment and therapy of complicating factors (e.g., malnutrition, sarcopenia, frailty or osteoporosis) have to be improved.

[Complex regional pain syndrome-An interdisciplinary view from the surgical consultation]. / Das komplexe regionale Schmerzsyndrom ­ eine interdisziplinäre Betrachtung aus der chirurgischen Sprechstunde.

Chronic pain disorders are common and have a substantial impact on the patients' daily life. The specific syndrome of complex regional pain syndrome (CRPS, Sudeck's disease) is comparatively rare and characterized by additional sensorimotor, vascular and trophic dysfunctions. The diagnosis is made based on the Budapest criteria and according to clinical symptoms. According to the German national guidelines, multimodal therapy includes drug, rehabilitative and psychosomatic approaches for the reduction of pain and restoration of functionality. Bisphosphonates, steroids and antiepileptic drugs are well-established as medicinal treatment but should always be used in combination with functional therapy. Interventional treatment options are reserved for patients with complicated and enduring symptoms and should be carried out in specialized centers. The course of the disease is highly individual and frequently requires a long-term interdisciplinary treatment.

Severe Traumatic Injury Induces Phenotypic and Functional Changes of Neutrophils and Monocytes.

BACKGROUND: Severe traumatic injury has been associated with high susceptibility for the development of secondary complications caused by dysbalanced immune response. As the first line of the cellular immune response, neutrophils and monocytes recruited to the site of tissue damage and/or infection, are divided into three different subsets according to their CD16/CD62L and CD16/CD14 expression, respectively. Their differential functions have not yet been clearly understood. Thus, we evaluated the phenotypic changes of neutrophil and monocyte subsets among their functionality regarding oxidative burst and the phagocytic capacity in severely traumatized patients. METHODS: Peripheral blood was withdrawn from severely injured trauma patients (TP; n = 15, ISS ≥ 16) within the first 12 h post-trauma and from healthy volunteers (HV; n = 15) and stimulated with fMLP and PMA. CD16dimCD62Lbright (immature), CD16brightCD62Lbright (mature) and CD16brightCD62Ldim (CD62Llow) neutrophil subsets and CD14brightCD16- (classical), CD14brightCD16+ (intermediate) and CD14dimCD16+ (non-classical) monocyte subsets of HV and TP were either directly analyzed by flow cytometry or the examined subsets of HV were sorted first by fluorescence-activated cell sorting and subsequently analyzed. Subset-specific generation of reactive oxygen species (ROS) and of E. coli bioparticle phagocytosis were evaluated. RESULTS: In TP, the counts of immature neutrophils were significantly increased vs. HV. The numbers of mature and CD62Ldim neutrophils remained unchanged but the production of ROS was significantly enhanced in TP vs. HV and the stimulation with fMLP significantly increased the generation of ROS in the mature and CD62Ldim neutrophils of HV. The counts of phagocyting neutrophils did not change but the mean phagocytic capacity showed an increasing trend in TP. In TP, the monocytes shifted toward the intermediate phenotype, whereas the classical and non-classical monocytes became less abundant. ROS generation was significantly increased in all monocyte subsets in TP vs. HV and PMA stimulation significantly increased those level in both, HV and TP. However, the PMA-induced mean ROS generation was significantly lower in intermediate monocytes of TP vs. HV. Sorting of monocyte and neutrophil subsets revealed a significant increase of ROS and decrease of phagocytic capacity vs. whole blood analysis. CONCLUSIONS: Neutrophils and monocytes display a phenotypic shift following severe injury. The increased functional abnormalities of certain subsets may contribute to the dysbalanced immune response and attenuate the antimicrobial function and thus, may represent a potential therapeutic target. Further studies on isolated subsets are necessary for evaluation of their physiological role after severe traumatic injury.

Optimal ligand discrimination by asymmetric dimerization and turnover of interferon receptors.

In multicellular organisms, antiviral defense mechanisms evoke a reliable collective immune response despite the noisy nature of biochemical communication between tissue cells. A molecular hub of this response, the interferon I receptor (IFNAR), discriminates between ligand types by their affinity regardless of concentration. To understand how ligand type can be decoded robustly by a single receptor, we frame ligand discrimination as an information-theoretic problem and systematically compare the major classes of receptor architectures: allosteric, homodimerizing, and heterodimerizing. We demonstrate that asymmetric heterodimers achieve the best discrimination power over the entire physiological range of local ligand concentrations. This design enables sensing of ligand presence and type, and it buffers against moderate concentration fluctuations. In addition, receptor turnover, which drives the receptor system out of thermodynamic equilibrium, allows alignment of activation points for ligands of different affinities and thereby makes ligand discrimination practically independent of concentration. IFNAR exhibits this optimal architecture, and our findings thus suggest that this specialized receptor can robustly decode digital messages carried by its different ligands.

Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung Injury.

BACKGROUND: Recently, identification of immunosuppressive polymorphonuclear leukocytes (PMNL) that were traditionally described as proinflammatory cells emerged in the field of posttraumatic immunity. To understand their local and remote distribution after trauma, PMNL-subsets and the impact of immunomodulatory Club Cell protein (CC)16 that correlates with pulmonary complications were assessed. METHODS: C57BL/6N mice were divided into three groups, receiving isolated blunt chest trauma (TxT), undergoing TxT followed by cecal ligation and puncture (CLP, TxT + CLP) after 24 h, or sham undergoing analgosedation (n = 18/group). Further, each group was subdivided into three groups receiving either no treatment (ctrl) or intratracheal neutralization of CC16 by application of anti-CC16-antibody or application of an unspecific IgG control antibody (n = 6/group). Treatment was set at the time point after TxT. Analyses followed 6 h post-CLP. PMNL were characterized via expression of CD11b, CD16, CD45, CD62L, and Ly6G by flow cytometry in bone marrow (BM), blood, spleen, lung, liver, and bronchoalveolar and peritoneal lavage fluid (BALF and PL). Apoptosis was assessed by activated (cleaved) caspase-3. Results from untreated ctrl and IgG-treated mice were statistically comparable between all corresponding sham, TxT, and TxT + CLP groups. RESULTS: Immature (CD16dimCD62Lbright) PMNL increased significantly in BM, circulation, and spleen after TxT vs. sham and were significantly attenuated in the lungs, BALF, PL, and liver. Classical-shaped (CD16brightCD62Lbright) PMNL increased after TxT vs. sham in peripheral tissue and were significantly attenuated in circulation, proposing a trauma-induced migration of mature or peripheral differentiation of circulating immature PMNL. Immunosuppressive (CD16brightCD62Ldim) PMNL decreased significantly in the lungs and spleen, while they systemically increased after TxT vs. sham. CLP in the TxT + CLP group reduced immunosuppressive PMNL in PL and increased their circulatory rate vs. isolated TxT, showing local reduction in affected tissue and their increase in nonaffected tissue. CC16 neutralization enhanced the fraction of immunosuppressive PMNL following TxT vs. sham and decreased caspase-3 in the lungs post-CLP in the TxT + CLP group, while apoptotic cells in the liver diminished post-TxT. Posttraumatic CC16 neutralization promotes the subset of immunosuppressive PMNL and antagonizes their posttraumatic distribution. CONCLUSION: Since CC16 affects both the distribution of PMNL subsets and apoptosis in tissues after trauma, it may constitute as a novel target to beneficially shape the posttraumatic tissue microenvironment and homeostasis to improving outcomes.

Single-molecule stretching experiments of flexible (wormlike) chain molecules in different ensembles: Theory and a potential application of finite chain length effects to nick-counting in DNA.

We propose a formalism for deriving force-elongation and elongation-force relations for flexible chain molecules from analytical expressions for their radial distribution function, which provides insight into the factors controlling the asymptotic behavior and finite chain length corrections. In particular, we apply this formalism to our previously developed interpolation formula for the wormlike chain end-to-end distance distribution. The resulting expression for the asymptotic limit of infinite chain length is of similar quality to the numerical evaluation of Marko and Siggia's variational theory and considerably more precise than their interpolation formula. A comparison to numerical data suggests that our analytical finite chain length corrections achieve a comparable accuracy. As an application of our results, we discuss the possibility of inferring the time-dependent number of nicks in single-molecule stretching experiments on double-stranded DNA from the accompanying changes in the effective chain length.