Pathological Fracture of the Femur Following Chronic Osteomyelitis: A Case Report of This Rare Presentation in Adults.

Chronic osteomyelitis is a common presentation in orthopaedics, particularly in the context of deep abscesses. Fractures related to osteomyelitis can be seen in children but are rare in adults. We present the rare case of a pathological fracture related to osteomyelitis in a 53-year-old warehouse worker who was previously fit and well. He presented with a right-sided thigh abscess and after initial surgical management, further imaging detailed osteomyelitis that was treated with suppressive antimicrobial therapy. Seven months after discharge, the patient presented to our emergency department with a right-sided proximal fracture of the femur. Retrospectively, we were able to localise the fracture site to the site of the previous cloaca from the osteomyelitis. We discuss whether prophylactic fixation is required for patients with extensive cloaca following a chronic fracture.

Introducing Ag Dopants into CdSe Nanoplatelets (NPLs) Leads to Effective Charge Separation for Better Photodetector Performance.

Solution-processed colloidal cadmium chalcogenide nanoplatelets (NPLs)--based photodetectors (PD) are promising materials for next-generation optoelectronic devices due to their excellent optical properties. Here, we report on ultrafast carrier relaxation dynamics of four monolayer (4 ML) Ag-doped CdSe (Ag: CdSe) NPLs using ultrafast transient absorption spectroscopy and their photodetectors applications. A broad dopant emission is observed at around 650 nm with a large FWHM of ~431 meV and band edge emission at 515 nm. The intragap dopant state acts as a hole acceptor, which leads to better charge separation. The ultrafast transient absorption spectroscopy study shows faster carrier recombination dynamics with a hole transfer time scale of ~10 ps in Ag-doped CdSe NPLs. This supports the excited hole capture phenomenon at the dopant state. Ag-doped CdSe NPLs-based PD performed better than undoped CdSe NPLs with detectivity and responsivity values of 1.3×1010 Jones and 2.4 mA/W, respectively.

Estimating nitric oxide (NO) from MDSCs by Griess method.

The functional importance of nitric oxide (NO) in the fields of immunology concerning its antimicrobial, anti-tumoral, anti-inflammatory, and immunosuppressive effects have made it inevitable to study its secretion from various cells. Nitrogen oxide synthase (NOS) is the enzyme responsible for synthesizing NO and its three isoforms function in a cell-dependent manner. NO is oxidized rapidly to Reactive nitrogen oxide species (RNOS) through which the roles of NO are being carried out. One of the major immune cells secreting NO is myeloid-derived suppressor cells (MDSCs). The function of these MDSCs in the suppression of T-cell proliferation as well as T-cell differentiation is found to be dependent on NO secretion. Apart from T-cell suppressive activity, NO is also known to interfere with natural killer (NK) cell functions. A convenient method to estimate NO secretion is by using Griess reagent named after Johann Peter Griess. In this method, NO reacts with the reagents to form a colored azo dye detectable using a microplate reader at a wavelength of 548nm. In this chapter, we summarized the detailed method of estimating NO from MDSCs by the Griess method.

Transition Metal Ions Influence the Performance of Photodetector of Two-Dimensional CdS Nanoplatelets.

Transition metal-doped two-dimensional (2D) semiconductor nanoplatelets (NPLs) with atomically precise thickness have attracted much research interest due to their inherent photo-physical properties. In this work, we have synthesized 2D Cu-doped CdS NPLs, investigated the charge transfer dynamics using ultrafast transient absorption spectroscopy, and fabricated an efficient photodetector device. A large Stoke's shifted emission at ~685 nm with an average lifetime of about ~1.45 µs is observed in Cu-doped CdS NPLs. Slower bleach recovery kinetics leads to large charge carrier separation in Cu-doped NPLs which is beneficial for photodetector applications. Cu-doped NPLs-based photodetectors exhibit high photocurrent, fast response (~120 ms), ~600 times higher photoresponsivity, and ~300 times higher detectivity (~4.1×1013 Jones) than undoped CdS NPLs. These excellent properties of Cu-doped CdS NPLs make this material an efficient alternative for next-generation optoelectronic devices.

Administration of soluble gp130Fc disrupts M-1 macrophage polarization, dendritic cell activation, MDSC expansion and Th-17 induction during experimental cerebral malaria.

Regulatory effect of IL-6 on various immune cells plays a crucial role during experimental cerebral malaria pathogenesis. IL-6 neutralization can restore distorted ratios of myeloid dendritic cells and plasmacytoid dendritic cells as well as the balance between Th-17 and T-regulatory cells. IL-6 can also influence immune cells through classical and trans IL-6 signalling pathways. As trans IL-6 signalling is reportedly involved during malaria pathogenesis, we focused on studying the effects of trans IL-6 signalling blockade on various immune cell populations and how they regulate ECM progression. Results show that administration of sgp130Fc recombinant chimera protein lowers the parasitemia, increases the survivability of Plasmodium berghei ANKA infected mice, and restores the distorted ratios of M1/M2 macrophage, mDC/pDC, and Th-17/Treg. IL-6 trans signalling blockade has been found to affect both expansion of myeloid derived suppressor cells (MDSCs) and expression of inflammatory markers on them during Plasmodium berghei ANKA infection indicating that trans IL-6 signalling might regulate various immune cells and their function during ECM. In this work for the first time, we delineate the effect of sgp130Fc administration on influencing the immunological changes within the host secondary lymphoid organ during ECM induced by Plasmodium berghei ANKA infection.

CD4+IL9+ (Th9) cells as the major source of IL-9, potentially modulate Th17/Treg mediated host immune response during experimental cerebral malaria.

Th9, a new subgroup of CD4+T cells is characterized by its specific cytokine IL-9, is a critical factor in allergic diseases, cancers and parasitic infections. This study aimed to explore the potential roles of Th9 cells in the immunopathogenesis of ECM. In splenocytes sourced from uninfected, PbA and Py infected mice, Th9 cells were characterised by flow cytometry, cell sorting and qPCR. Enhancement of CD4+IL-9+ (Th9) cells were observed in both the infections, which corroborated with increased expression of the differentiating transcription factors. Moreover, crucial cytokine receptors (IL-4R, TGF-ßR, IL-6R) as well as chemokine receptors (CCR3, CCR6 and CCR7) and activation marker (CD96), demonstrated elevation upon PbA infection in splenic Th9 cells. Furthermore, Neutralization of IL-9 along with IL-6 enhanced host survivability, reduced mean neurological score of ECM. However, anti- IL-9 treatment also down regulated frequency of Th17 cells, and its transcription factors pSTAT3, RORγT along with depleted Il-1ß and Il-6 expression. In sum, understanding how IL-9 producing CD4+ T-cells can alter Th17/Treg ratio and by that modulate host's immune response, could pave the way for developing immunomodulatory interventions against cerebral malaria.

IL-6 dependent expansion of inflammatory MDSCs (CD11b+ Gr-1+) promote Th-17 mediated immune response during experimental cerebral malaria.

Myeloid derived suppressor cells (MDSCs) are a group of heterogeneous cell populations that can suppress T cell responses. Various aspects of MDSCs in regulating immune responses in several cancer and infectious diseases have been reported till date. But the role and regulation of MDSCs have not been systematically studied in the context of malaria. This study depicts the phenotypic and functional characteristics of splenic MDSCs and how they regulate Th-17 mediated immune response during Experimental Cerebral Malaria (ECM). Flow cytometric analysis reveals that MDSCs in the spleen and bone marrow expand at 8 dpi during ECM. Among subtypes of MDSCs, PMN-MDSCs show significant expansion in the spleen but M-MDSCs remain unaltered. Functional analysis of sorted MDSCs from spleens of Plasmodium berghei ANKA (PbA) infected mice shows suppressive nature of these cells and high production of Nitric oxide (NO). Besides, MDSCs were also found to express various inflammatory markers during ECM suggesting the M1 type phenotype of these cells. In-vivo depletion of MDSCs by the use of Anti Gr-1 increases mice survival but doesn't significantly alter the parasitemia. Previously, it has been reported that Treg/Th-17 balance in the spleen is skewed towards Th-17 during ECM. Depletion of MDSCs was found to regulate Th-17 percentages to homeostatic levels and subvert various inflammatory changes in the spleen. Among different factors, IL-6 was found to play an important role in the expansion of MDSCs and expression of inflammatory markers on MDSCs in a STAT3-dependent manner. These findings provide a unique insight into the role of IL-6 in the expansion of the MDSC population which causes inflammatory changes and increased Th-17 responses during ECM.

Patients With Un-Displaced Or Displaced Intra Capsular Proximal Femur Fractures Do Not Represent A Different Patient Group And Have Similar Short And Long Term Mortality.

BACKGROUND: Proximal femur fractures in geriatric patients are associated with substantial mortality. Management of intracapsular proximal femur fractures has been based on age, displacement, cognition, and pre-injury mobility. However, over the last decade, there has been a tendency to offer arthroplasty rather than internal fixation for these patients irrespective of displacement, to allow early mobilisation and negate the higher rate of reoperation due to failed internal fixation. There are no previous investigations analysing whether the severity of fracture displacement is related to different patient characteristics. AIM: This study examines whether patients sustaining undisplaced or displaced intracapsular proximal femur fractures represent different patient groups with different pre-injury characteristics and post-operative mortality, irrespective of treatment modality. METHODS: A retrospective series of 329 consecutive patients over the age of 55 years who sustained intracapsular proximal femur fractures, who underwent surgical management at a district general hospital over a period of 2 years (2012-2013) were identified using the national hip fracture database. Demographics, American Society of Anaesthesiologist (ASA) grade, pre-injury outdoor mobility status, cognitive status, and admission serum investigations, fracture displacement, type of surgery, and mortality rates at short term (2 years) & long-term (7-9 years) were reviewed. RESULTS: There were 109 male and 220 female patients with a minimum follow-up of 7 years. The mean age at surgery was 81.6 years (range 55-103 years). There were 63 (19.1%) undisplaced fractures (Garden 1 &2) and, 265 (80.5%) displaced fractures (Garden 3 & 4). The median survival in this cohort was 2.95 years (95% CI 2.3-3.6). Mortality rates were 77.4% (n=257) at long-term (7-9 years) follow-up. Admission patient characteristics showed no statistically significant difference between displaced and undisplaced fracture groups. This included ASA, pre-operative cognition, and mobility status. Fracture displacement was not an independent predictor of mortality at short or long term. CONCLUSION: In patients sustaining intracapsular proximal femur fractures, the degree of displacement is not a caveat for a different patient group. Fracture displacement is not predicted by the pre-injury level of function and does not predict short or long-term mortality.

"Surgically Treated COVID-19-Positive Trauma Patients Had a Higher Fatality Rate" - A Rural District General Hospital's Perspective in the United Kingdom.

Introduction Our study analyses the influence of the COVID-19 pandemic on perioperative death in elderly patients undergoing surgery for fractures who test positive for the virus during their admission in a rural hospital setting in the UK. Methods One hundred and fifty-six consecutive patients with age more than 75 years, who underwent surgery for fractures in Glangwili General Hospital during the second wave of the pandemic between 20th November 2020 and 20th January 2021, were included in this study. The 28-day mortality rate was estimated, and the results were compared to a matched cohort of patients from a similar duration before the pandemic (20th November 2019 to 20th January 2020). Results A total of 41 out of 156 patients were tested positive for COVID-19 in this study cohort. The overall 28-day mortality rate was 8.9% (n=15 patients) in comparison to 4% (n=8) in the comparative cohort of 196 patients from the pre-pandemic era. Of the 41 patients who tested positive for COVID-19, 11 patients died within 28 days of surgery, resulting in a mortality rate of 26.8% with a relative risk of 7.7(p=0.0461). Furthermore, 91% (n=10) of COVID-19-positive patients who died had an underlying cardiac disease and/or proximal femoral fractures. The 28-day mortality rate in those tested negative for COVID-19 was 3.5% (n=4). Conclusion There is a significantly increased risk of death in the perioperative period on contracting COVID-19, in patients who are 75 years of age or older, especially those with associated cardiac comorbidities and who have sustained proximal femoral fractures.

Partial impairment of late-stage autophagic flux in murine splenocytes leads to sqstm1/p62 mediated nrf2-keap1 antioxidant pathway activation and induced proteasome-mediated degradation in malaria.

Splenomegaly, a major symptom in Plasmodium infection, is extensively studied for its immunopathological role in mice malaria model infected with Plasmodium berghei ANKA. The status of autophagic regulation in hosts in malaria pathogenesis remains unreported till date. This study demonstrated the autophagy, proteasomal degradation and NRF2-KEAP1 antioxidant pathway status in the host during Plasmodium infection taking murine spleen as our organ of interest. Initial staining and autophagic gene expression indicate a possibility of autophagic pathway activation. Although the conversion of LC3A to LC3B and lysosome-autophagosome fusion increases, the final degradation step remains incomplete. Resultant upregulation of p62 and its altered phosphorylated status enhances its binding to keap1 causing NRF2 translocation to the nucleus. NRF2 act as transcription factor upregulating p62 level itself leading to an autoinduction loop of p62 expression. Interestingly, enhancement of P62 interaction with proteasome subunit RPT1 indicates a possible role in transporting ubiquitinated cargo to proteasome complex. Ubiquitination level increased with subsequent upregulation of all three modes of proteasomal degradation i.e trypsin-like, caspase-like and especially chymotrypsin-like. Sqstm1/p62 plays a critical central role in regulating autophagy, proteasomal degradation, and NRF2-KEAP1 pathway. The incomplete autophagic flux in the final step may be a key therapeutic target, as autophagic degradation and subsequent pathogenic peptide presentation is of utmost necessity for downstream immune response.

Understanding Painful Hip in Young Adults: A Review Article.

A wide number of disorders, including pathologies outside the hip, can cause and refer pain to hip. However, determining the cause of a painful hip can be a major challenge to orthopedic surgeons. Failure to diagnose and appropriately investigate pathologies of the hip in adults may result in delayed management and prolonged patient morbidity. A systematic approach to investigating the etiology of hip pain in adults (e.g., history, careful clinical and radiographic examination), will help identify the majority of clinically important pathologies which can cause hip pain. Conservative treatment and selective use of injection therapies has proven quite successful for the treatment of most causes of hip pain.

Autophagic induction modulates splenic plasmacytoid dendritic cell mediated immune response in cerebral malarial infection model.

Splenic plasmacytoid dendritic cells (pDC) possess the capability to harbor live replicative Plasmodium parasite. Isolated splenic pDC from infected mice causes malaria when transferred to naïve mice. Incomplete autophagic degradation might cause poor antigen processing and poor immune response. Induction of autophagic flux by rapamycin treatment led to better prognosis by boosting pDC centered immune response against the pathogen. Splenic pDC from rapamycin-treated infected mice, caused less parasitemia in naïve mice. The downregulation of adhesion with unaltered phagocytic potential of the cells post autophagic induction restricted excessive parasite burden within them. Rapamycin-treated pDC played a better role in antigen presentation. They showed higher expression of co-stimulatory molecules CD80, CD86, DEC205, MHCI. Rapamycin-treated pDC induced CD28 expression on CD8+ T cells and suppressed FasL level. This cells also influenced differentiation of effector, memory T cell population. The increase in IL10: TNFα ratio, Treg: Th17 ratio and lowering of myeloid DC: plasmacytoid DC ratio was observed. It shifted the overaggressive inflammation mediated Th1 pathway that is reported to incur host damage, to a better well-balanced cytokine profile exhibiting Th2 pathway. Autophagic flux induction within pDC proved to be beneficial in combating malarial pathogenicity.

Impact of autophagic regulation on splenic red pulp macrophages during cerebral malarial infection.

Splenic red pulp macrophages play a critical role infiltration of infected RBC and elimination of pathogens during malarial infection. However, the efficiency of pathogenic processing and the intricate pathway followed by them to boost the downstream immune response has not been studied in details. We checked the status of autophagic regulation within the cells both before and after the infection and also modulated the autophagic flux with either its inducer or inhibitor. We found that the upregulation of autophagic gene and the corresponding pathway is correlated with better parasite clearance and survivability, with an enhanced downstream immune response. It also increases their phagocytic potential with better Lysosomal associated protein I and II synthesis. The autophagolysosome formation increases as well, and more vacuole bound LC3B protein are detected. Chemokine synthesized from Red Pulp macrophage helps in mediating the induction for recruiting neutrophil and CD4 + T cells to the splenic red pulp region. The skewing of M1 macrophage polarity is observed post autophagic induction with a better costimulatory molecule like CD80, CD86 expression and antigen presenting molecule MHC I, MHC II is observed. This study shows the possibility of an alternative or adjuvant therapy regimen for the malarial patient by inducing the autophagic pathway that targets the red pulp macrophages. This might be helpful for better pathogen degradation and processing. The subsequent clearance of parasite will result in a better outcome for the patients.