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Abstract. Objectives:. The number of geriatric hip fracture patients is high and expected to rise in the coming years, and many are frail and at risk for adverse outcomes. Early identification of high-risk patients is crucial to balance treatment and optimize outcome, but remains challenging. Previous research in patients with multitrauma suggested that neutrophil phenotype analysis could aid in early identification of high-risk patients. This pilot study investigated the feasibility and clinical value of neutrophil phenotype analysis in geriatric patients with a hip fracture. Methods:. A prospective study was conducted in a regional teaching hospital in the Netherlands. At the emergency department, blood samples were collected from geriatric patients with a hip fracture and analyzed using automated flow cytometry. Flow cytometry data were processed using an automated clustering algorithm. Neutrophil activation data were compared with a healthy control cohort. Neutrophil phenotype categories were assessed based on two-dimensional visual assessment of CD16/CD62L expression. Results:. Blood samples from 45 geriatric patients with a hip fracture were included. Neutrophils showed an increased activation profile and decreased responsiveness to formyl peptides when compared to healthy controls. The neutrophil phenotype of all patients was categorized. The incidence of severe adverse outcome was significantly different between the different categories (P = 0.0331). Moreover, patients with neutrophil phenotype category 0 developed no severe adverse outcomes. Conclusions:. Using point-of-care fully automated flow cytometry to analyze the neutrophil compartment in geriatric hip fracture patients is feasible and holds clinical value in determining patients at risk for adverse outcome. This study is a first step toward immuno-based precision medicine for identifying geriatric hip fracture patients that are deemed fit for surgery.

Clavicle fractures are the most common fracture in the human body, accounting for 5–10% of all fractures presenting to the Emergency Department. The treatment of clavicle fractures historically has been more on the conservative side, but there has been recent evidence that operative management could reduce the incidence of adverse outcomes post-fracture. This review focuses on analysing the previous and present scientific literature on post-operative and post-conservative clavicle complications. This review concludes that the evidence for surgical management of clavicle fractures with certain indications is controversial and further studies are required.

Abstract Background Inadequate activation of the innate immune system after trauma can lead to severe complications such as Acute Respiratory Distress Syndrome and Multiple Organ Dysfunction Syndrome. The spleen is thought to modulate the cellular immune system. Furthermore, splenectomy is associated with improved outcome in severely injured trauma patients. We hypothesized that a splenectomy alters the cellular immune response in polytrauma. Methods All adult patients with an ISS ≥ 16 and suffering from splenic or hepatic injuries were selected from our prospective trauma database. Absolute leukocyte numbers in peripheral blood were measured. White blood cell kinetics during the first 14 days were compared between splenectomized patients, patients treated surgically for liver trauma and nonoperatively treated individuals. Results A total of 129 patients with a mean ISS of 29 were included. Admission characteristics and leukocyte numbers were similar in all groups, except for slightly impaired hemodynamic status in patients with operatively treated liver injuries. On admission, leukocytosis occurred in all groups. During the first 24 h, leukopenia developed gradually, although significantly faster in the operatively treated patients. Thereafter, leukocyte levels normalized in all nonoperatively treated cases whereas leukocytosis persisted in operatively treated patients. This effect was significantly more prominent in splenectomized patients than all other conditions. Conclusions This study demonstrates that surgery for intra-abdominal injuries is associated with an early drop in leucocyte numbers in peripheral blood. Moreover, splenectomy in severely injured patients is associated with an altered cellular immune response reflected by a persistent state of prominent leukocytosis after trauma.

IntroductionExtensive trauma surgery evokes an immediate cellular immune response including altered circulatory neutrophil numbers. The concurrent bone marrow (BM) response however is currently unclear. We hypothesize that these BM changes include (1) a relative reduction of the bone marrow neutrophil fraction and (2) increasing heterogeneity of the bone marrow neutrophil pool due to (3) the appearance of aged/returning neutrophils from circulation into the BM-compartment.Materials and MethodsEight pigs were included in a standardized extensive trauma surgery model. Blood and bone marrow samples were collected at baseline and after 3 hours of ongoing trauma surgery. Leukocyte and subtype counts and cell surface receptor expression levels were studied by flow cytometry.ResultsAll animals survived the interventions. A significant drop in circulating neutrophil counts from 9.3 to 3.2x106 cells/ml (P=0.001) occurred after intervention, whereas circulatory neutrophil cell surface expression of CD11b increased. The concurrent bone marrow response included an increase of the BM neutrophil fraction from 63 ± 3 to 71 ± 3 percent (P

Abstract Backgrounds Splenic injury accounts for 40% of all injuries after blunt abdominal trauma. Blunt splenic injury in hemodynamically unstable patients is preferably treated by splenectomy. Nowadays hemodynamically stable patients with low grade splenic injuries are mostly treated by non-operative management (NOM). However no consensus exists about the management of high grade splenic injuries in hemodynamically stable patients. Therefore the aim of this study was to analyze patients with high grade splenic injuries in our institution. Methods We retrospectively included all patients with a splenic injury presented to our level I trauma center during the 5-year period from January 1, 2012, until December 31, 2017. Baseline characteristics, data regarding complications and mortality were collected from the electronic patient registry. Patients were grouped based on splenic injury and the treatment they received. Results A total of 123 patients were included, of which 93 (75.6%) were male with a median age of 31 (24–52) and a median injury severity score of 27 (17–34). High grade injuries (n = 28) consisted of 20 Grade IV injuries and 8 grade V injuries. Splenectomy was required in 15/28 (53.6%) patients, of whom all remained hemodynamically unstable after resuscitation, including all grade V injuries. A total of 13 patients with high grade injuries were treated with spleen preserving therapy. Seven of these patients received angio-embolization. One patient went for laparotomy and the spleen was treated with a hemostatic agent. Secondary hemorrhage was present in 3 of these patients (initial treatment: 1 embolization/ 2 observational), resulting in a success rate of 76.9%. There is no mortality seen in patient with high grade splenic injuries. Conclusion Non-operative treatment in high grade splenic injuries is a safe treatment modality in hemodynamically stable patients. Hemodynamic status and peroperative bleeding, not injury severity or splenic injury grade were the drivers for surgical management by splenectomy. This selected cohort of patients must be closely monitored to prevent adverse outcomes from secondary delayed bleeding in case of non-operative management.

Abstract Background Patients often develop infectious complications after severe trauma. No biomarkers exist that enable early identification of patients who are at risk. Neutrophils are important immune cells that combat these infections by phagocytosis and killing of pathogens. Analysis of neutrophil function used to be laborious and was therefore not applicable in routine diagnostics. Hence, we developed a quick and point-of-care method to assess a critical part of neutrophil function, neutrophil phagosomal acidification. The aim of this study was to investigate whether this method was able to analyze neutrophil functionality in severely injured patients and whether a relation with the development of infectious complications was present. Results Fifteen severely injured patients (median ISS of 33) were included, of whom 6 developed an infection between day 4 and day 9 after trauma. The injury severity score did not significantly differ between patients who developed an infection and patients who did not (p = 0.529). Patients who developed an infection showed increased acidification immediately after trauma (p = 0.006) and after 3 days (p = 0.026) and a decrease in the days thereafter to levels in the lower normal range. In contrast, patients who did not develop infectious complications showed high-normal acidification within the first days and increased tasset to identify patients at risk for infections after trauma and to monitor the inflammatory state of these trauma patients. Conclusion Neutrophil function can be measured in the ICU setting by rapid point-of-care analysis of phagosomal acidification. This analysis differed between trauma patients who developed infectious complications and trauma patients who did not. Therefore, this assay might prove a valuable asset to identify patients at risk for infections after trauma and to monitor the inflammatory state of these trauma patients. Trial registration Central Committee on Research Involving Human Subjects, NL43279.041.13. Registered 14 February 2014. https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm .

Abstract Background Treatment of blunt splenic injury has changed over the past decades. Nonoperative management (NOM) is the treatment of choice. Adequate patient selection is a prerequisite for successful NOM. Impaired mental status is considered as a relative contra indication for NOM. However, the impact of altered consciousness in well-equipped trauma institutes is unclear. We hypothesized that impaired mental status does not affect outcome in patients with splenic trauma. Methods Our prospectively composed trauma database was used and adult patients with blunt splenic injury were included during a 14-year time period. Treatment guidelines remained unaltered over time. Patients were grouped based on the presence (Group GCS:

At homeostasis the vast majority of neutrophils in the circulation expresses CD16 and CD62L within a narrow expression range, but this quickly changes in disease. Little is known regarding the changes in kinetics of neutrophils phenotypes in inflammatory conditions. During acute inflammation more heterogeneity was found, characterized by an increase in CD16dim banded neutrophils. These cells were probably released from the bone marrow (left shift). Acute inflammation induced by human experimental endotoxemia (LPS model) was additionally accompanied by an immediate increase in a CD62Llow neutrophil population, which was not as explicit after injury/trauma induced acute inflammation. The situation in sub-acute inflammation was more complex. CD62Llow neutrophils appeared in the peripheral blood several days (>3 days) after trauma with a peak after 10 days. A similar situation was found in the blood of COVID-19 patients returning from the ICU. Sorted CD16low and CD62Llow subsets from trauma and COVID-19 patients displayed the same nuclear characteristics as found after experimental endotoxemia. In diseases associated with chronic inflammation (stable COPD and treatment naive HIV) no increases in CD16low or CD62Llow neutrophils were found in the peripheral blood. All neutrophil subsets were present in the bone marrow during homeostasis. After LPS rechallenge, these subsets failed to appear in the circulation, but continued to be present in the bone marrow, suggesting the absence of recruitment signals. Because the subsets were reported to have different functionalities, these results on the kinetics of neutrophil subsets in a range of inflammatory conditions contribute to our understanding on the role of neutrophils in health and disease.

Abstract Background Trauma leads to a complex inflammatory cascade that induces both immune activation and a refractory immune state in parallel. Although both components are deemed necessary for recovery, the balance is tight and easily lost. Losing the balance can lead to life-threatening infectious complications as well as long-term immunosuppression with recurrent infections. Neutrophils are known to play a key role in these processes. Therefore, this review focuses on neutrophil characteristics and function after trauma and how these features can be used to identify trauma patients at risk for infectious complications. Results Distinct neutrophil subtypes exist that play their own role in the recovery and/or development of infectious complications after trauma. Furthermore, the refractory immune state is related to the risk of infectious complications. These findings change the initial concepts of the immune response after trauma and give rise to new biomarkers for monitoring and predicting inflammatory complications in severely injured patients. Conclusion For early recognition of patients at risk, the immune system should be monitored. Several neutrophil biomarkers show promising results and analysis of these markers has become accessible to such extent that they can be used for point-of-care decision making after trauma.

Background: Coronavirus disease of 2019 (COVID-19) is associated with a prothrombotic state and a high incidence of thrombotic event(s) (TE).Objectives: To study platelet reactivity in hospitalized COVID-19 patients and determine a possible association with the clinical outcomes thrombosis and all-cause mortality.Methods: Seventy nine hospitalized COVID-19 patients were enrolled in this retrospective cohort study and provided blood samples in which platelet reactivity in response to stimulation with ADP and TRAP-6 was determined using flow cytometry. Clinical outcomes included thrombotic events, and all-cause mortality.Results: The incidence of TE in this study was 28% and all-cause mortality 16%. Patients that developed a TE were younger than patients that did not develop a TE [median age of 55 vs. 70 years; adjusted odds ratio (AOR) = 0.96 per 1 year of age, 95% confidence interval (CI) 0.92–1.00; p = 0.041]. Furthermore, patients using preexisting thromboprophylaxis were less likely to develop a thrombotic complication than patients that were not (18 vs. 54%; AOR = 0.19, 95% CI 0.04–0.84; p = 0.029). Conversely, having asthma strongly increased the risk on TE development (AOR = 6.2, 95% CI 1.15–33.7; p = 0.034). No significant differences in baseline P-selectin expression or platelet reactivity were observed between the COVID-19 positive patients (n = 79) and COVID-19 negative hospitalized control patients (n = 21), nor between COVID-19 positive survivors or non-survivors. However, patients showed decreased platelet reactivity in response to TRAP-6 following TE development.Conclusion: We observed an association between the use of preexisting thromboprophylaxis and a decreased risk of TE during COVID-19. This suggests that these therapies are beneficial for coping with COVID-19 associated hypercoagulability. This highlights the importance of patient therapy adherence. We observed lowered platelet reactivity after the development of TE, which might be attributed to platelet desensitization during thromboinflammation.

Leukocyte viability (determined by e.g. propidium iodide [PI] staining) is automatically measured by hematology analyzers to check for delayed bench time. Incidental findings in fresh blood samples revealed the existence of leukocytes with decreased viability in critically ill surgical patients. Not much is known about these cells and their functional and/or clinical implications. Therefore, we investigated the incidence of decreased leukocyte viability, the implications for leukocyte functioning and its relation with clinical outcomes. An automated alarm was set in a routine hematology analyzer (Cell-Dyn Sapphire) for the presence of non-viable leukocytes characterized by increased fluorescence in the PI-channel (FL3:630±30nm). Patients with non-viable leukocytes were prospectively included and blood samples were drawn to investigate leukocyte viability in detail and to investigate leukocyte functioning (phagocytosis and responsiveness to a bacterial stimulus). Then, a retrospective analysis was conducted to investigate the incidence of fragile neutrophils in the circulation and clinical outcomes of surgical patients with fragile neutrophils hospitalized between 2013-2017. A high FL3 signal was either caused by 1) neutrophil autofluorescence which was considered false positive, or by 2) actual non-viable PI-positive neutrophils in the blood sample. These two causes could be distinguished using automatically generated data from the hematology analyzer. The non-viable (PI-positive) neutrophils proved to be viable (PI-negative) in non-lysed blood samples, and were therefore referred to as 'fragile neutrophils'. Overall leukocyte functioning was not impaired in patients with fragile neutrophils. Of the 11 872 retrospectively included surgical patients, 75 (0.63%) were identified to have fragile neutrophils during hospitalization. Of all patients with fragile neutrophils, 75.7% developed an infection, 70.3% were admitted to the ICU and 31.3% died during hospitalization. In conclusion, fragile neutrophils occur in the circulation of critically ill surgical patients. These cells can be automatically detected during routine blood analyses and are an indicator of critical illness.

Abstract Background Nonoperative management for blunt splenic injury is the preferred treatment. To improve the outcome of selective nonoperative therapy, the current challenge is to identify factors that predict failure. Little is known about the impact of concomitant injury on outcome. Our study has two goals. First, to determine whether concomitant injury affects the safety of selective nonoperative treatment. Secondly we aimed to identify factors that can predict failure. Methods From our prospective trauma registry we selected all nonoperatively treated adult patients with blunt splenic trauma admitted between 01.01.2000 and 12.21.2013. All concurrent injuries with an AIS ≥ 2 were scored. We grouped and compared patients sustaining solitary splenic injuries and patients with concomitant injuries. To identify specific factors that predict failure we used a multivariable regression analysis. Results A total of 79 patients were included. Failure of nonoperative therapy (n = 11) and complications only occurred in patients sustaining concomitant injury. Furthermore, ICU-stay as well as hospitalization time were significantly prolonged in the presence of associated injury (4 versus 13 days,p

Abstract Background The Regulatory Focus Questionnaire (RFQ) assesses regulatory promotion and prevention focus, which represent orientations towards gains or losses. The main objective of this study was to examine the psychometric properties of the newly translated German version. Methods A sample of 1024 participants answered the questionnaire and several related instruments. We used an online survey tool to collect this data. Data analysis was conducted using methods of exploratory and confirmatory factor analysis in SPSS and AMOS. Results The RFQ displayed acceptable reliability, while its correlations with other, related psychological constructs indicated good validity. Factor analysis showed good fit for a two-dimensional model. Tests of measurement invariance revealed clear evidence for metric invariance while scalar invariance remained uncertain. Differences in regulatory focus based on sociodemographic characteristics are reported and discussed. Conclusions Overall, the RFQ can be recommended for application in fields dealing with motivation and goal attainment in a broad sense.

Abstract Background Selective non-operative management (NOM) for the treatment of blunt splenic trauma is safe. Currently, the feasibility of selective NOM for penetrating splenic injury (PSI) is unclear. Unfortunately, little is known about the success rate of spleen-preserving surgical procedures. The aim of this study was to investigate the outcome of selective NOM for penetrating splenic injuries. Methods A dual-centre study is performed in two level-one trauma centres. All identified patients treated for PSI were identified. Patients were grouped based on the treatment they received. Group one consisted of splenectomised patients, the second group included patients treated by a spleen-preserving surgical intervention, and group three included those patients who were treated by NOM. Results A total of 118 patients with a median age of 27 and a median ISS of 25 (interquartile range (IQR) 16–34) were included. Ninety-six patients required operative intervention, of whom 45 underwent a total splenectomy and 51 underwent spleen-preserving surgical procedures. Furthermore, 22 patients (12 stab wounds and 10 gunshot wounds) were treated by NOM. There were several anticipated significant differences in the baseline encountered. The median hospitalization time was 8 (5–12) days, with no significant differences between the groups. The splenectomy group had significantly more intensive care unit (ICU) days (2(0–6) vs. 0(0–1)) and ventilation days (1(0–3) vs. 0(0–0)) compared to the NOM group. Mortality was only noted in the splenectomy group. Conclusions Spleen-preserving surgical therapy for PSI is a feasible treatment modality and is not associated with increased mortality. Moreover, a select group of patients can be treated without any surgical intervention at all.

Research has shown that Westerners expect less change to occur in the future than they recall having occurred in the past. The present research investigated how recalled change and anticipated change may vary across cultures. Because Chinese perceive past times as being closer to the present than do Westerners, and people believe things tend to change more over a long period of time than over a short period of time, Chinese may perceive smaller changes from the past to the present than do Westerners. Consequently, the asymmetry between recalled change and anticipated change would disappear for Chinese. Four empirical studies revealed that for British participants, recalled changes in the past for personality, values, and the person as a whole were greater than anticipated changes in the future, whereas for Chinese, recalled changes in the past were similar in magnitude as anticipated changes in the future. Studies 2b and 3 further revealed that subjective temporal distance accounted for the cross-cultural differences in the asymmetry between recalled and anticipated changes.

Beehive products such as honey, beeswax and recently pollen have been regarded for many years as appropriate sentinels for environmental pesticide pollutions. However, despite yearly application of hundreds of approved pesticides in agricultural fields, only a minor fraction of these organic compounds were actually detected in honey and beeswax samples. This observation has led us to question the general suitability of beehive products as a sentinel for synthetic organic pesticides applied in the field. The aim of the present study was to experimentally determine the distribution (logarithmic ratio of beeswax to honey pesticide concentration, LogD) and depletion kinetics (half-life) of selected pesticides in honey and beeswax as a measure of the latter matrixes to serve as a pesticide sentinel. The obtained parameters were used to extrapolate to pesticide burden in honey and beeswax samples collected from German and Israeli apiaries. In addition, we aimed to establish a mathematical model, enabling us to predict distribution of selected pesticides between honey to beeswax, by utilizing simple substance descriptors, namely, octanol/water partitioning coefficient, molar weight and Henry coefficient. Based on the present results, it appears that pesticides with LogD values > 1 and half-life in beeswax > 1 day, were likely to accumulate and detected in beeswax samples, and less likely to be found in honey. On the other hand, pesticides with negative LogD values were highly likely to be found in honey and less so in beeswax samples. Finally, pesticides with LogD values between 0-1 were expected to be found in both matrixes. The developed model was successfully applied to predict LogD values, thereby identifying octanol/water partitioning and molar weight as the most prominent substance descriptors, which affect pesticide distribution between honey and beeswax.

A malfunction of the innate immune response in COVID-19 is associated with eosinopenia, particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils. Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16, and CD62L) in the absence or presence of a formyl peptide (fNLF). Forty-five SARS-CoV-2 PCR positive patients were grouped based on disease severity. PCR negative patients with proven bacterial (n = 20) or other viral (n = 10) infections were used as disease controls. Eosinophils were identified with the use of the FlowSOM algorithm. Low blood eosinophil numbers (p < 0.005) were found both in patients with COVID-19 and with other infectious diseases, albeit less pronounced. Two discrete eosinophil populations were identified in healthy controls both before and after activation with fNLF based on the expression of CD11b. Before activation, the CD11bbright population consisted of 5.4% (CI95% = 3.8, 13.4) of total eosinophils. After activation, this population of CD11bbright cells comprised nearly half the population (42.21%, CI95% = 35.9, 54.1). Eosinophils in COVID-19 had a similar percentage of CD11bbright cells before activation (7.6%, CI95% = 4.5, 13.6), but were clearly refractory to activation with fNLF as a much lower percentage of cells end up in the CD11bbright fraction after activation (23.7%, CI95% = 18.5, 27.6; p < 0.001). Low eosinophil numbers in COVID-19 are associated with refractoriness in responsiveness to fNLF. This might be caused by migration of fully functional cells to the tissue.

Postharvest application of fungicides is commonly applied in order to reduce food loss. Prochloraz is currently the only postharvest fungicide registered in Israel and Europe in avocado fruits. Due to its unfavorable toxicological properties, prochloraz will be banned from the end of 2020 for future postharvest usage and therefore a substitute candidate is urgently warranted. Fludioxonil, a relatively safe, wide spectrum fungicide, is approved in Europe and Israel for postharvest use in various fruits, but not avocado. Hence, fludioxonil has been evaluated in the present study as a potential substitute for prochloraz in avocado. The objectives of the present study were to determine fludioxonil efficacy against common fungal infestations in avocado and distribution kinetics between peel and pulp in comparison to prochloraz. At the same concentration range (75−300 µg/L), fludioxonil was as effective as prochloraz in inhibiting postharvest decay, while in the early season cultivars, suffering mainly from stem-end rot, it exhibited a better decay control than prochloraz. Fludioxonil and prochloraz displayed negligible and undetected pulp levels, respectively, due to low peel penetrability. Taken altogether, fludioxonil was found to be a suitable candidate for replacing prochloraz as a postharvest fungicide in avocado.

The Health Regulatory Focus Scale (HRFS) is a short scale which measures an individual's prevention and promotion focus in a health-specific context. The main objective of this study was to examine the psychometric properties of the newly translated German version of the HRFS. Reliability and item characteristics were found to be satisfactory. Validity of both subscales toward other psychological constructs including behavioral approach and avoidance, core self-evaluations, optimism, pessimism, neuroticism, as well as several measures of physical and mental health was shown. In addition, invariance of the measure across age and gender groups was shown. Exploratory as well as confirmatory factor analyses clearly indicated a two-factorial structure with a moderate correlation between the two latent constructs. Differences in health promotion and prevention focus between socio-demographic groups are discussed. The HRFS is found to be a valid and reliable instrument for the assessment of regulatory focus in health-related environments.

Summary: In this case report we describe a rare case of bilateral diaphragmatic dysfunction due to Lyme disease. Case report: A 62-years-old male presented to the hospital because of flu-like symptoms. During initial evaluation a bilateral diaphragmatic weakness with orthopnea and nocturnal hypoventilation was observed, without a known aetiology. Bilateral diaphragmatic paralysis was confirmed by fluoroscopy with a positive sniff test. The patient was referred to our centre for chronic non-invasive nocturnal ventilation (cNPPV). Subsequent investigations revealed evidence of anti-Borrelia seroactivity in EIA-IgG and IgG-blot, suggesting a recent infection with Lyme disease, and resulted in a 4-week treatment with oral doxycycline. The symptoms of nocturnal hypoventilation were successfully improved with cNPPV. However, our patient still shows impaired diaphragmatic function but he is no longer fully dependent on nocturnal ventilatory support. Conclusion: Lyme disease should be considered in the differential diagnosis of diaphragmatic dysfunction. It is a tick-borne illness caused by one of the three pathogenic species of the spirochete Borrelia burgdorferi, present in Europe. A delay in recognizing the symptoms can negatively affect the success of treatment. Non-invasive mechanical ventilation (NIV) is considered a treatment option for patients with diaphragmatic paralysis.

A series of reactive molecular dynamics simulations is used to study the internal structure of incipient soot particles obtained from acetylene pyrolysis. The simulations were performed using the ReaxFF potential at four different temperatures. The resulting soot particles are cataloged and analyzed to obtain statistics of their mass, volume, density, C/H ratio, number of cyclic structures, and other features. A total of 3324 incipient soot particles were analyzed in this study. Based on their structural characteristics, the incipient soot particles are classified into two classes, termed type 1 and type 2 incipient soot particles in this work. The radial distribution of density, cyclic (5-, 6-, or 7-member rings) structures, and C/H ratio inside the particles revealed a clear difference in the internal structure between type 1 and type 2 particles. These classes were further found to be well represented by the size of the particles, with smaller particles in type 1 and larger particles in type 2. The radial distributions of ring structures, density, and the C/H ratio indicated the presence of a dense core region in type 2 particles. In contrast, no clear evidence of the presence of a core was found in type 1 particles. In type 2 incipient soot particles, the boundary between the core and shell was found to be around 50-60% of the particle's radius of gyration.

Background: The routine use of multimodal analgesic modality results in lower pain scores with minimum side effects and opioid utilization., Materials and Methods:  A prospective, cross-sectional, observational study was conducted among orthopedicians practicing across India to assess the professional opinions on using analgesics to manage orthopedic pain effectively., Results:  A total of 530 orthopedicians participated in this survey. Over 50% of the participants responded that tramadol with or without paracetamol was the choice of therapy for acute pain. Nearly 50% of the participants mentioned that multimodal interventions can sometimes help to manage pain. A total of 55.6% of participants mentioned that using Non-steroidal anti-inflammatory drugs was the most common in their clinical practice, while 25.7% of participants mentioned that they used tramadol more commonly in their clinical practice. As per clinical efficacy ranking, the combination of tramadol plus paracetamol (44.3%) was ranked first among analgesic combinations, followed by aceclofenac plus paracetamol (40.0%). The severity of pain (62.6%) followed by age (60.6%) and duration of therapy (52.6%) were the most common factors that should be considered while prescribing tramadol plus paracetamol combination. Gastrointestinal and renal are reported as the most common safety concerns encountered with analgesics., Conclusion:  The combination of tramadol and paracetamol was identified as the most preferred choice of analgesics for prolonged orthopedic pain management., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Bedi et al.)

In this study, we evaluated the changes in air pollutant concentrations around Milwaukee, WI, during and after lockdown due to the COVID-19 pandemic for a period of 126 days. Measurements of particulate matter (PM 1 , PM 2.5 , and PM 10 ), NH 3 , H 2 S, and O 3  + NO 2 , were made on a 74-km route of arterial and highway roads from April to August 2020 using a Sniffer 4D sensor mounted to a vehicle. Traffic volume during measurement periods were estimated from smartphone-based traffic data. From lockdown (March 24, 2020-June 11, 2020) to post-lockdown (June 12, 2020-August 26, 2020) median traffic volume increased roughly 30-84%, depending upon the road type. In addition, increases in mean concentrations of NH 3 (277%), PM (220-307%), and O 3  + NO 2 (28%) were also observed. For both traffic and air pollutants, abrupt changes in the data were observed mid-June, shortly after lockdown measures were lifted in Milwaukee County. Indeed, traffic was able to explain up to 57% of PM, 47% of NH 3 , and 42% of O 3  + NO 2 variance in pollutant concentrations on arterial and highway road segments. Two arterial roads that did not have statistically significant changes in traffic patterns during the lockdown exhibited no statistically significant trends between traffic and air quality parameters. This study demonstrated that COVID-19 lockdowns in Milwaukee, WI, caused significant decreases in traffic, which in turn had a direct impact on air pollutants. It also highlights the need for traffic volume and air quality data at relevant spatial and temporal scales for accurately assessing source apportionment of combustion-based air pollutants, which cannot be captured with typical ground-based sensor systems., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Pseudomyxoma Peritonei (PMP) is a mucin producing cancer with appendix as primary site. Cytoreductive Surgery (CRS) combined with hyper-thermic intraperitoneal chemotherapy (HIPEC) is an established form of therapy known to prolong survival in patients with PMP and peritoneal carcinomatosis. Methods/patients In our case series, we present five cases of PMP with synchronous liver and peritoneal metastasis treated with CRS and HIPEC. It is a very rare condition which needs more research to be able to comment on overall survival., Results: However, in our study, we found lower age, female gender and complete cytoreduction in surgery to be favourable predictors for improved morbidity., Conclusion: In our experience, CRS/HIPEC seem to be feasible for patients with PMP with synchronous liver and peritoneal metastasis., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Standard mitral valve replacement in patients with chronic mitral valve regurgitation and mitral valve stenosis consistently results in a decrease in early postoperative left ventricular ejection performance. Some studies showed that preservation of mitral valve leaflet and subvalvular apparatus can reduce postoperative left ventricular dysfunction. On the basis of the concept, this randomized clinical trial comparing mitral valve replacement with preservation of mitral subvalvular apparatus and conventional mitral valve replacement performed in National Institute of Cardiovascular Diseases (NICVD), Dhaka, Bangladesh, in the period of July 2010 to December 2011. We included 60 patients of mitral regurgitation and mitral stenosis, among them 30 patients underwent mitral valve replacement with preservation of mitral subvalvular apparatus (Group A) and 30 patients underwent conventional mitral valve replacement (Group B). There was no significant difference between two groups in terms of peri-operative variables. But there was significant higher incidence of Low cardiac output (LOS) syndrome [36.7% vs. 6.9% (p<0.05)] and congestive heart failure in Group B than Group A. The duration of ICU stay was also significantly higher in conventional mitral valve replacement group [113.23±11.30 hours vs. 96.23±20.02 (p=0.001)]. Additionally, there was significantly less fall of left ventricular ejection fraction in preservation of mitral subvalvular apparatus group [preop 65.27±5.45, at discharge 54.31±3.78, after 3 months 58.28±5.20 (p<0.0001)] than conventional group [preop 66.43±4.58, at discharge 46.43±3.87, after 3 months 46.55±3.63 (p<0.0001)]. In this study left ventricular ejection fraction was used as measure of left ventricular function. We postulate that, this relative preservation of left ventricular ejection fraction was likely the result of preservation of mitral subvalvular apparatus.

This study investigates stabilization of graphene oxide (GO) nanosheets in polyethylene oxide-polypropylene oxide (PEO-PPO) block copolymers (P103, P123 and F127). Changes in micellization of copolymers upon GO addition were monitored using dynamic light (DLS) and small angle neutron scattering (SANS). Structural developments at sheet surface were studied with two possibilities; (i) adsorption of PPO block over hydrophobic basal plane allowing the engagement of hydrophilic PEO with aqueous bulk, and (ii) adsorption of micelles mediated via carboxylated groups. Insignificant changes in micellar parameters for P123 and P127 were indicative of their inferior interaction with GO. On the other hand, P103 micelles exhibited high affinity for sheets, noticeable as emergence of mass fractals and more than two-fold enhancement in micelle number density. The latter allowed coverage of entire surface with P103 micelles. Existence of mass fractals was verified by extracting the form and structure factors from the fitted SANS data. Spectroscopic and thermogravimetric analyses illustrated non-covalent adsorption of copolymer aggregates. It was interesting to note that the dispersion remained stable against protein and electrolyte addition. A comprehensive understanding on colloidal stability can be valuable for drug delivery applications of GO sheets., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A 29-year-old woman with recurrent pelvic pain that progressed post partum was diagnosed with a multicystic pararectal lesion on ultrasound and CT scan. Physiology was conducted to establish a preoperative function and pudendal nerve integrity. The lesion was resected using a Da Vinci Xi robotic system. She recovered uneventfully with complete resolution of her symptoms. Hindgut cysts most often arise in the presacral space as the result of incomplete embryogenesis. Patients may present with various non-specific symptoms. Although the majority are benign, resection is recommended, as there is a 30%-43% risk of malignancy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Large-bowel obstruction caused by volvulus is potentially life threatening if not managed promptly. Sigmoid colon is the most common site of volvulus followed by caecum. Synchronous double colonic volvulus is an exceedingly rare entity, with only five cases published previously. We present the case of a 77-year-old man with a synchronous sigmoid and caecal volvulus. He underwent total colectomy with ileostomy formation with a view to reverse the ileostomy at a later date., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Unlabelled: Cleavage and polyadenylation specificity factor subunit 6 (CPSF6), a host factor that interacts with the HIV-1 capsid (CA) protein, is implicated in diverse functions during the early part of the HIV-1 life cycle, including uncoating, nuclear entry, and integration targeting. Preservation of CA binding to CPSF6 in vivo suggests that this interaction is fine-tuned for efficient HIV-1 replication in physiologically relevant settings. Nevertheless, this possibility has not been formally examined. To assess the requirement for optimal CPSF6-CA binding during infection of primary cells and in vivo, we utilized a novel CA mutation, A77V, that significantly reduced CA binding to CPSF6. The A77V mutation rendered HIV-1 largely independent from TNPO3, NUP358, and NUP153 for infection and altered the integration site preference of HIV-1 without any discernible effects during the late steps of the virus life cycle. Surprisingly, the A77V mutant virus maintained the ability to replicate in monocyte-derived macrophages, primary CD4(+) T cells, and humanized mice at a level comparable to that for the wild-type (WT) virus. Nonetheless, revertant viruses that restored the WT CA sequence and hence CA binding to CPSF6 emerged in three out of four A77V-infected animals. These results suggest that the optimal interaction of CA with CPSF6, though not absolutely essential for HIV-1 replication in physiologically relevant settings, confers a significant fitness advantage to the virus and thus is strictly conserved among naturally circulating HIV-1 strains., Importance: CPSF6 interacts with the HIV-1 capsid (CA) protein and has been implicated in nuclear entry and integration targeting. Preservation of CPSF6-CA binding across various HIV-1 strains suggested that the optimal interaction between CA and CPSF6 is critical during HIV-1 replication in vivo Here, we identified a novel HIV-1 capsid mutant that reduces binding to CPSF6, is largely independent from the known cofactors for nuclear entry, and alters integration site preference. Despite these changes, virus carrying this mutation replicated in humanized mice at levels indistinguishable from those of the wild-type virus. However, in the majority of the animals, the mutant virus reverted back to the wild-type sequence, hence restoring the wild-type level of CA-CPSF6 interactions. These results suggest that optimal binding of CA to CPSF6 is not absolutely essential for HIV-1 replication in vivo but provides a fitness advantage that leads to the widespread usage of CPSF6 by HIV-1 in vivo., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Purpose: To report 22 patients who underwent repair of compound Achilles tendon ruptures with peroneus brevis tendon augmentation., Methods: Records of 6 women and 19 men aged 21 to 42 (mean, 28) years who underwent repair of compound Achilles tendon ruptures with peroneus brevis tendon augmentation were reviewed. All the wounds were transverse/oblique, minimally contaminated, and could be closed primarily. Patients were evaluated at months 3, 9, and 12, using the Foot and Ankle Outcome Score (FAOS) questionnaire., Results: Of the 22 patients, 3 developed superficial skin complications that healed gradually, and 2 developed a superficial discharging sinus and underwent minor debridement. No patient had a re-rupture of the Achilles tendon. At the one-year follow-up, all patients achieved good functional outcome in terms of the FAOS., Conclusion: Repair of Achilles tendon ruptures with peroneus brevis tendon augmentation achieved good functional outcome.

Perioperative instrument breakage is not an infrequent occurrence, even for experienced surgeons. The most commonly reported instrument breaks in orthopedic procedures are drill bits, followed by Kirschner wires and cannulated guide pins. The reasons for failure include improper technique and repetitive use. The retrieval of broken hardware can be technically challenging, particularly if the fragment has become embedded in bone. Retrieval methods have been described for cannulated guide pin fragments in the hip; however, no specific techniques have been described for the retrieval of guide pin fragments embedded in the bones of the foot. In the present report, we describe a technique we have found useful for retrieval of a guide pin fragment that had broken off during a Lisfranc fracture repair 6 weeks earlier. The technique was used in a delayed situation; however, we believe it would be even easier to use during an intraoperative breakage., (Copyright © 2014 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Simultaneous bilateral avulsion fracture of the tibial tuberosity is a rare injury. Since the first reported case in the 1950s only 21 such cases have been reported in literature. When they do occur, it is usually in an adolescent athletic male, generally in the absence of any underlying pathology although rarely it may be associated with an underlying connective tissue disorder. The age range of the injury corresponds to the time of growth plate closure and maturation of the fibro-cartillagenous attachment of the tuberosity. Most of the fractures require open reduction and internal fixation and usually heal well without any significant complications., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Ankle fractures are extremely common. However, the outcomes of operatively treated bimalleolar and trimalleolar ankle fractures remain unclear. We aimed to evaluate and compare the functional outcomes of operatively treated bimalleolar versus trimalleolar ankle fractures and the ability of patients to return to sporting activities., Methods: A retrospective review of all patients with operatively treated ankle fractures for a period of 2 years was performed. Demographics, fracture pattern, operative details, postoperative radiographs, and complications were extracted and analyzed statistically. Outcome variables were union rates, pain ratings using the visual analogue scale (VAS) and the Olerud and Molander (O&M) score, ability to return to sporting activities, satisfaction with surgery, and surgical complications., Results: Forty-seven patients with bimalleolar and trimalleolar ankle fractures were recruited. At 1 year postoperatively, most patients regained good function and had good to excellent O&M scores. There were no notable differences in terms of VAS and O&M scores for both the bimalleolar and trimalleolar group. However, 26 (55.3%) of 47 patients had residual pain. Twenty-nine (61.7%) patients complained of stiffness, and 21 (44.7%) patients had ankle swelling. Of 33 (70.2%) patients who were involved in sporting activities prior to the ankle injury, 9 of 33 (27.3%) were able to return to preinjury level of sporting activities with no difficulties. Of the 33 patients, 18.2% were unable to do sports activities at all., Conclusion: The majority of our patients recovered well in their second year despite some residual deficits. We found no difference in functional outcome between bimalleolar and trimalleolar ankle fractures, although it is of great concern that a notable number of patients will not return to sporting activities. Residual symptoms and functional limitation after ankle fracture must be emphasized to patients to manage postoperative expectations., Level of Evidence: Level II, retrospective case series.

The Akin osteotomy is a frequently performed medial closing wedge osteotomy of the proximal phalanx of the hallux. It is usually used as a complimentary procedure in the correction of hallux valgus. Various implants and techniques have been described for fixation. Suture fixation has the advantage of a lower implant signature and a reduction in cost. However, the thin cortex of the phalanx can be prone to failure during suture application. We describe a new technique for suture fixation, which we have found to be reliable and to reduce the risk of phalangeal cortical failure., (Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The surgical stress of total knee arthroplasty (TKA) procedure and the application of intra-operative pneumatic thigh tourniquet increases local fibrinolytic activity, which contributes significantly to post-operative blood loss. Tranexamic acid, an antifibrinolytic drug, is commonly used to control post-operative blood loss. The recommended mode of administration of tranexamic acid is either oral or intravenous. However, the mechanism of action of the tranexamic acid points towards the possible effectiveness it may have following local/intra-articular application. This prospective, double-blinded, randomized preliminary study evaluated the efficacy of intra-articular tranexamic acid in reducing TKA-associated post-operative blood loss., Methods: Fifty consenting patients with osteoarthritis of the knee scheduled for primary unilateral cemented-TKA were randomly allocated to one of the two groups: Tranexamic Acid (TA) group (n = 25, 500 mg/5 ml tranexamic acid) and the control group (n = 25, 5 ml 0.9% saline). The drug and control solution were administered intra-articularly through the drain tube immediately after the wound closure. Parameters related to blood loss (drop in haemoglobin, haematocrit differential) and the drain output [volume (ml)] were compared between the two groups., Results: On a comparative basis, TA-group obtained significant reduction in the drain output [95% CI: 360.41-539.59, p < 0.001] at 48 h post-operatively. Even though the control group received sixfold more blood transfusion than TA-group, it showed a greater drop in haemoglobin and haematocrit (p < 0.05)., Conclusions: Local application of tranexamic acid seems to be effective in reducing post-TKA blood loss as well as blood transfusion requirements., Level of Evidence: Therapeutic study, Level II.

Coli surface antigen 6 (CS6) is a widely expressed enterotoxigenic Escherichia coli (ETEC) colonization factor that mediates bacterial attachment to the small intestinal epithelium. CS6 is a polymer of two protein subunits CssA and CssB, which are secreted and assembled on the cell surface via the CssC/CssD chaperone usher (CU) pathway. Here, we present an atomic resolution model for the structure of CS6 based on the results of X-ray crystallographic, spectroscopic and biochemical studies, and suggest a mechanism for CS6-mediated adhesion. We show that the CssA and CssB subunits are assembled alternately in linear fibres by the principle of donor strand complementation. This type of fibre assembly is novel for CU assembled adhesins. We also show that both subunits in the fibre bind to receptors on epithelial cells, and that CssB, but not CssA, specifically recognizes the extracellular matrix protein fibronectin. Taken together, structural and functional results suggest that CS6 is an adhesive organelle of a novel type, a hetero-polyadhesin that is capable of polyvalent attachment to different receptors., (© 2012 Blackwell Publishing Ltd.)

The antiepileptic drugs are known to alter the bone metabolism and result in various range of pathological conditions (osteoporosis, osteomalacia, vitamin D deficiency, secondary hyperparathyroidism). These clinical conditions developed either due to direct effect of these therapeutic agents on bone or due to alteration in the homeostasis of other regulators of bone metabolism like serum calcium, vitamin D, and parathyroid hormone. Long-term therapy with antiepileptic agents results in higher incidence of pathological fracture, which is a consequence of either osteoporotic or osteomalasic (secondary to vitamin D deficiency) changes in bone produced by these drugs. Secondary hyperparathyroidism due to vitamin D deficiency following long-term polytherapy of antiepileptic drug ultimately leading to development of brown tumor and pathological fracture is very unusual.

Alendronate is considered to be the gold standard drug for the treatment of postmenopausal osteoporosis. A 75 years old female presented with diaphyseal fracture following trivial fall. Though this fracture pattern was reported in the western world its presence among the population of this subcontinent is very rare. Radiographs showed a transverse fracture in diaphyseal area with lateral cortical thickening and medial spiking. History confirmed that patient was on long term bisphosphonate therapy. Opposite femur also showed lateral cortical thickening at the same level as was seen on fractured side. Biochemical picture was complicated with secondary (Vitamin-D deficiency) hyperparathyroidism. Fracture was fixed with Locking Compression plate and allogenic bone grafting was done. Prophylactic nailing was done on the contralateral side. Vitamin-D and calcium deficiency was corrected and subcutaneous Teriparatide was started. Radiographic evidence of callus formation is present but confirmation of union is uncertain.

The antiulcer and in vitro anti-inflammatory activities of the aerial parts of Enicostemma littorale against aspirin, ethanol, and pyloric ligation-induced ulcers in rats and bovine serum albumin denaturation were studied. The extract (200 mg/kg and 400 mg/kg po) was administered to the overnight fasted rats, one hour prior to aspirin / alcohol / pyloric ligation challenge. The ulcer index, tissue GSH levels, and lipid peroxidation levels were estimated in all the models of ulcers and the volume of gastric secretion, acidity, and pH, were estimated in the pyloric ligation model of ulcers. Pretreatment with the extract showed a dose-dependent decrease in the ulcer index (Against Aspirin, ethanol challenge, and pyloric ligation. The prior administration of the extract also reduced the total acidity, free acidity, and volume of gastric secretion, and elevated the gastric pH. In addition, it was also observed that the extract inhibited the serum albumin denaturation in a dose-dependent manner. It may be concluded that the methanolic extract possesses antiulcer activity, and the anti-inflammatory activity of the extract may be attributed to the antioxidant potential, as reported earlier.

Phlebotomus argentipes Annandale and Brunetti (Diptera: Psychodidae) is the vector for visceral leishmaniasis in India. The aspects of its biology such as feeding and man vector contact are associated with emergence periodicity of the adult. Hence, the present study was made to find out the actual emergence period of P. argentipes. Wild caught P. argentipes were confined in the rearing pots inside laboratory. The newly emerged adults were collected at hourly intervals and released in to separate polythene bags and were held at 4°C till death. Sand flies were segregated sex-wise after the death under a microscope. The emergence of adult was observed throughout the day. However, the male preferred dawn emergence and the female the dusk. Two peaks of emergence were found in a day; first one in the morning (0900h) and the second one in the evening (1800h). The ratio of both sexes was found to be about equal. The emergence of adult was found to be 77% out of total eggs laid, which was completed within 7-10 days from the 1st day of emergence under laboratory conditions (25°C to 31°C and 70% to 75% relative humidity). This study has important bearings to find out the actual time for personal protection against biting of sand flies to prevent the transmission of Kala-azar.