Prospective observational study evaluating the outcome of a fixed angle plate (proximal humerus internal locking system) in proximal humerus fractures

Background: Proximal humerus fractures are common among elderly. The present study assesses the functional outcomes of fixed angle plate (proximal humerus internal locking system (PHILOS)) in fractures of proximal humerus.Methods: 30 participants aged ≥18 years with proximal humerus fracture (2, 3 and 4 part) who underwent PHILOS fixation were enrolled. Undisplaced, open, severely comminuted, metastatic, and pathological fractures and with associated head injury and neurovascular injuries wew excluded. Clinical and radiological evaluation were done pre and post-operatively. Intraarticular extent of fracture geometry was assessed using 3-dimensional computed tomography. Participants were managed preoperatively with analgesics and shoulder immobilizer followed by preanesthetic check-up and routine investigations and surgery was done once participants were stable. Sample size was calculated assuming excellent or satisfactory results in 80% participants 6 months after surgery, relative precision of 20%, α of 5% and 10% attrition rate. Institutional ethics committee approved the study and written informed consent was obtained from all study participants.Results: Mean age of study participants was 62.9 (14.9) years and were predominantly females (66.6%, n=20). No significant difference between type of fracture and duration of recovery was observed (p=0.4). 30% participants had post-operative complications, stiffness was the most common (13.3%, n=4) complication. 76.6% (n=23) participants had good functional outcomes. Significant correlation between type of fracture and NEER score was observed (p<0.0001).Conclusions: PHILOS is a preferential implant in proximal humerus fractures due to angular stability, particularly in comminuted fractures in younger patients, and osteoporotic fractures in elderly, thus allowing early mobilization and satisfactory final functional outcome.

A Clinicopathological study of Fungal Diseases in Patients with Chronic Rhinosinusitis and Sinonasal Polyposis

INTRODUCTION: Fungi have been implicated in the etiopathogenesis of chronic rhinosinusitis with nasal polyposis. In an era with AIDS, broad spectrum antibiotic therapy, cytotoxic drugs, steroid therapy and the organ transplantations, fungal infections are becoming increasingly common and very diverse. The most common site of fungal infections in man is the lung with or without haematogenous spread to other organs. But localised fungal infections can also occur in the upper respiratory tract and is more common than was previously suspected. FUNGAL SPECIES: The common fungal infection which affect the nose and sinuses are Candidiasis, Aspergillosis, Phycomycosis, Actinomycosis, Coccidioidomycosis, Histoplasmosis, Cryptococcosis, Blastomycosis, Sporotrichosis and Nocardiosis. FUNGAL SINUSITIS: Fungus is ubiquitous, present in all our surroundings and the air we inhale.Most healthy people do not react to the presence of fungus due to functioning immune system. However, in rare instances,fungus may cause inflammation in the nose and sinuses. Fungal sinusitis may come in different forms, differing in pathology, symptoms, course, severity and the treatment required. CLASSIFICATION OF FUNGAL RHINOSINUSITIS: Fungal Rhinosinusitis is broadly classified into 2 groups 1) INVASIVE, 2) NON INVASIVE INVASIVE diseases include: a) Acute Invasive (Fulminant) Fungal Rhinosinusitis – Mucorales and Aspergillus. b) Granulomatous invasive Fungal rhinosinusitis – A.flavus c) Chronic invasive fungal rhinosinusitis – A.fumigatus NonInvasive diseases include: a) Fungal ball – A.fumigatus, A.flavus, Scedesporium b) Allergic fungal rhino-sinusitis – Bipolaris sp., Curvularia lunata, A.fumigatus. AIMS OF THE STUDY: To study the prevalence of Fungal Diseases in all cases of Sinonasal polyposis and chronic rhino-sinusitis admitted for Functional Endoscopic Sinus Surgery in our Hospital. OBJECTIVES: 1. To find out the prevalence of Fungal Sinusitis in cases of sinonasal polyposis/Chronic rhino-sinusitis. 2. To determine the presence of fungal organisms in Chronic rhinosinusitis associated with nasal polyposis by both KOH mount and fungal culture. 3. To identify the type of fungal sinusitis in sinonasal polyposis/Chronic rhino-sinusitis. 4. To identify the fungal isolates most common in chronic sinusitis and sinonasal polyposis. 5. To study the clinical and pathological manifestations of fungal infections of the nose and paranasal sinuses. 6. To find the association of Fungal sinusitis with Systemic diseases. MATERIALS AND METHODS: Specimen: sinus secretions and Polyps. Sample Size: 156. Patients of all age groups and of either sex who presented with radiologically proven sinusitis with symptoms > 12 weeks duration and undergoing functional endoscopic sinus surgery was included in the study. Patients were interviewed by structured questionnaire after obtaining informed consent. All the patients were also clinically assessed Inclusion Criteria: • All cases of CRS who underwent functional endoscopic sinussurgery in the department of ENT, TVMCH. • All age groups. • Both male & female. Exclusion Criteria: Patients who were on topical or systemic steroid for the past One month before the study period. All cases with characteristic appearance of fungi in DNE and during surgery. Cases with Clinically appearing Malignant Nasal mass and Rhinosporidiosis. Period of study: 2 years. Duration : November 2017 to June 2019. METHODS OF COLLECTION OF DATA. Detailed History taking and clinical examination. Relevant radiological investigations(CTscan). Obtaining a definitive diagnosis with the help of KOH mount and Fungal Culture reports. Sample collection and processing. During my study period , samples of nasal sinus tissue, sinus secretions and allergic mucin from patients undergoing FESS were subjected to mycological culture. The specimen was collected in sterile saline per operatively and taken to the microbiology lab as early as possible and was processed on the sameday. The sample was be subjected to direct microscopy with 10% potassium hydroxide and culture. RESULTS: In the present study 156 patients of chronic rhinosinusitis, majority of the patients were in the age group of 31 – 40 years. followed by 21-30 years.The mean age of the patients affected with fungal rhinosinusitis was 34.5 yrs. Males were predominant (55%) compared to females (45%). Male to female ratio was (1.3:1). The most common symptoms were nasal obstruction 85%, headache 56%, nasal discharge 24%, and sneezing 21%. In this study, 53 patients had nasal polyp 60 had deviated nasal septum, 15 patients had diabetes, 9 had hypertension and 4 had both. In this present study,out of 156 cases of chronic rhinosinusitis, prevalence of fungal rhinosinusitis was found to be 13%. In this study fungal positivity was found in 20 patients by direct examination (KOH mount) or culture In this study majority of the fungi isolated were Aspergillus species (90%) in particular A.flavus. Out of the 18 Aspergillus isolates 13 were Aspergillus flavus and 5 were Aspergillus fumigatus. CONCLUSION: The sinonasal mycotic infection accounts for 13% of chronic rhinosinusitis. The most commonly affected age group are the third and fourth decade. The sex ratio is more or less equal. Fungal sinusitis should be suspected in those patients with CRS presenting with signs and symptoms such as nasal obstruction, nasal polyps, nasal discharge. With the help of histopathological examination of all sinus specimens, CT scan, Diagnostic Nasal Endoscopy thediagnosis of CRS have become easier nowadays. Endoscopic sinus surgery followed by antifungal therapy role is the major treatment of fungal sinusitis. Due to the increased incidence in fungal infections of paranasal sinuses, the Otorhinolaryngolgists should keep fungal infections in their mind during their daily practice. In fungal sinusitis, unilateral involvement of paranasal sinuses is more common. Maxillary sinus is the most commonly affected sinus among all the paranasal sinuses in fungal rhinosinusitis

Development and Validation of a Smartphone Heart Rate Acquisition Application for Health Promotion and Wellness Telehealth Applications

Objective. Current generation smartphones' video camera technologies enable photoplethysmographic (PPG) acquisition and heart rate (HR) measurement. The study objective was to develop an Android application and compare HRs derived from a Motorola Droid to electrocardiograph (ECG) and Nonin 9560BT pulse oximeter readings during various movement-free tasks. Materials and Methods. HRs were collected simultaneously from 14 subjects, ages 20 to 58, healthy or with clinical conditions, using the 3 devices during 5-minute periods while at rest, reading aloud under observation, and playing a video game. Correlation between the 3 devices was determined, and Bland-Altman plots for all possible pairs of devices across all conditions assessed agreement. Results. Across conditions, all device pairs showed high correlations. Bland-Altman plots further revealed the Droid as a valid measure for HR acquisition. Across all conditions, the Droid compared to ECG, 95% of the data points (differences between devices) fell within the limits of agreement. Conclusion. The Android application provides valid HRs at varying levels of movement free mental/perceptual motor exertion. Lack of electrode patches or wireless sensor telemetric straps make it advantageous for use in mobile-cell-phone-delivered health promotion and wellness programs. Further validation is needed to determine its applicability while engaging in physical movement-related activities

Change in national, regional, and state-level pneumonia and severe pneumonia morbidity in India::modelled estimates for 2000 and 2015

Background: The absolute number of pneumonia deaths in India has declined substantially since 2000. However, pneumonia remains a major cause of morbidity in children in the country. We used a risk factor-based model to estimate pneumonia and severe pneumonia morbidity in Indian states in 2000 and 2015. Methods: In this modelling study, we estimated the burden of pneumonia and severe pneumonia in children younger than 5 years using a risk factor-based model. We did a systematic literature review to identify published data on the incidence of pneumonia from community-based longitudinal studies and calculated summary estimates. We estimated state-specific incidence rates for WHO-defined clinical pneumonia between 2000 and 2015 using Poisson regression and the prevalence of risk factors in each state was obtained from National Family Health Surveys. From clinical pneumonia studies, we identified studies reporting the proportion of clinical pneumonia cases with lower chest wall indrawing to estimate WHO-defined severe pneumonia cases. We used the estimate of the proportion of cases with lower chest wall indrawing to estimate WHO-defined severe pneumonia cases for each state. Findings: Between 2000 and 2015, the estimated number of pneumonia cases in Indian HIV-uninfected children younger than 5 years decreased from 83·8 million cases (95% uncertainty interval [UI] 14·0–300·8) to 49·8 million cases (9·1–174·2), representing a 41% reduction in pneumonia cases. The incidence of pneumonia in children younger than 5 years in India was 657 cases per 1000 children (95% UI 110–2357) in 2000 and 403 cases per 1000 children (74–1408) in 2015. The estimated national pneumonia case fatality rate in 2015 was 0·38% (95% UI 0·11–2·10). In 2015, the estimated number of severe pneumonia cases was 8·4 million (95% UI 1·2–31·7), with an incidence of 68 cases per 1000 children (9–257) and a case fatality ratio of 2·26% (0·60–16·30). In 2015, the estimated number of pneumonia cases in HIV-uninfected children was highest in Uttar Pradesh (12·4 million [95% UI 2·1–45·0]), Bihar (7·3 million [1·3–26·1]), and Madhya Pradesh (4·6 million [0·7–17·0]). Between 2000 and 2015, the greatest reduction in pneumonia cases was observed in Kerala (82% reduction). In 2015, pneumonia incidence was greater than 500 cases per 1000 children in two states: Uttar Pradesh (565 cases per 1000 children [95% UI 94–2047]) and Madhya Pradesh (563 cases per 1000 children [88–2084]). Interpretation: The estimated number of pneumonia and severe pneumonia cases among children younger than 5 years in India decreased between 2000 and 2015. Improvements in socioeconomic indicators and specific government initiatives are likely to have contributed to declines in the prevalence of pneumonia risk factors in many states. However, pneumonia incidence in many states remains high. The introduction of new vaccines that target pneumonia pathogens and reduce risk factors will help further reduce the burden of pneumonia in the country

Combinations of PARP Inhibitors with Temozolomide Drive PARP1 Trapping and Apoptosis in Ewing's Sarcoma.

Ewing's sarcoma is a malignant pediatric bone tumor with a poor prognosis for patients with metastatic or recurrent disease. Ewing's sarcoma cells are acutely hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition and this is being evaluated in clinical trials, although the mechanism of hypersensitivity has not been directly addressed. PARP inhibitors have efficacy in tumors with BRCA1/2 mutations, which confer deficiency in DNA double-strand break (DSB) repair by homologous recombination (HR). This drives dependence on PARP1/2 due to their function in DNA single-strand break (SSB) repair. PARP inhibitors are also cytotoxic through inhibiting PARP1/2 auto-PARylation, blocking PARP1/2 release from substrate DNA. Here, we show that PARP inhibitor sensitivity in Ewing's sarcoma cells is not through an apparent defect in DNA repair by HR, but through hypersensitivity to trapped PARP1-DNA complexes. This drives accumulation of DNA damage during replication, ultimately leading to apoptosis. We also show that the activity of PARP inhibitors is potentiated by temozolomide in Ewing's sarcoma cells and is associated with enhanced trapping of PARP1-DNA complexes. Furthermore, through mining of large-scale drug sensitivity datasets, we identify a subset of glioma, neuroblastoma and melanoma cell lines as hypersensitive to the combination of temozolomide and PARP inhibition, potentially identifying new avenues for therapeutic intervention. These data provide insights into the anti-cancer activity of PARP inhibitors with implications for the design of treatment for Ewing's sarcoma patients with PARP inhibitors.Research in the M.J.G. laboratory is supported by grants from the Wellcome Trust (086357 and 102696/Z/13/Z; http://www.wellcome.ac.uk/Funding). Research in the S.P.J. laboratory is funded by Cancer Research UK Program Grant C6/A11224 (http://www.cancerresearchuk.org/funding-for-researchers/our-funding-schemes), the European Research Council (http://erc.europa.eu/funding-and-grants)and the European Community Seventh Framework Program grant agreement no. HEALTH-F2-2010-259893 (DDResponse). Core infrastructure funding was provided by Cancer Research UK Grant C6946/A14492 and Wellcome Trust Grant WT092096. S.P.J. receives a salary from the University of Cambridge, supplemented by Cancer Research UK. J.T. was funded by the European Community Seventh Framework Program grant agreement no. HEALTH-F2-2010-259893 (DDResponse). U.M. is supported by a Cancer Research UK Clinician Scientist Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014098

Bioengineered small extracellular vesicles deliver multiple SARS‐CoV‐2 antigenic fragments and drive a broad immunological response

The COVID‐19 pandemic highlighted the clear risk that zoonotic viruses pose to global health and economies. The scientific community responded by developing several efficacious vaccines which were expedited by the global need for vaccines. The emergence of SARS‐CoV‐2 breakthrough infections highlights the need for additional vaccine modalities to provide stronger, long‐lived protective immunity. Here we report the design and preclinical testing of small extracellular vesicles (sEVs) as a multi‐subunit vaccine. Cell lines were engineered to produce sEVs containing either the SARS‐CoV‐2 Spike receptor‐binding domain, or an antigenic region from SARS‐CoV‐2 Nucleocapsid, or both in combination, and we tested their ability to evoke immune responses in vitro and in vivo. B cells incubated with bioengineered sEVs were potent activators of antigen‐specific T cell clones. Mice immunised with sEVs containing both sRBD and Nucleocapsid antigens generated sRBD‐specific IgGs, nucleocapsid‐specific IgGs, which neutralised SARS‐CoV‐2 infection. sEV‐based vaccines allow multiple antigens to be delivered simultaneously resulting in potent, broad immunity, and provide a quick, cheap, and reliable method to test vaccine candidates

Placental expression of eNOS, iNOS and the major protein components of caveolae in women with pre-eclampsia

Caveolae regulate many cardiovascular functions and thus could be of interest in relation to pre-eclampsia, a pregnancy specific disorder characterised by hypertension and proteinuria. We examined placental mRNA and protein expression/localisation of the caveolae components Caveolin 1-3, Cavin 1-4 as well as eNOS/ iNOS in normotensive control (n=24) and pre-eclamptic pregnancies (n=19). Placental mRNA expression of caveolin-1, cavin 1-3, was lower and eNOS expression was increased in pre-eclampsia (P<0.05 for all). Additionally Caveolin-1 protein expression was also reduced in pre-eclampsia (P=0.007); this could be an adaptive response in pre-eclampsia, possibly to attenuate the oxidative stress/inflammation

Data assimilation in the solar wind: challenges and first results

Data Assimilation (DA) is used extensively in numerical weather prediction (NWP) to improve forecast skill. Indeed, improvements in forecast skill in NWP models over the past 30 years have directly coincided with improvements in DA schemes. At present, due to data availability and technical challenges, DA is underused in space weather applications, particularly for solar wind prediction. This paper investigates the potential of advanced DA methods currently used in operational NWP centres to improve solar wind prediction. To develop the technical capability, as well as quantify the potential benefit, twin experiments are conducted to assess the performance of the Local Ensemble Transform Kalman Filter (LETKF) in the solar wind model ENLIL. Boundary conditions are provided by the Wang-Sheeley-Arge coronal model and synthetic observations of density, temperature and momentum generated every 4.5hr at 0.6AU. While in-situ spacecraft observations are unlikely to be routinely available at 0.6AU, these techniques can be applied to remote sensing of the solar wind, such as with Heliospheric Imagers or Interplanetary Scintillation. The LETKF can be seen to improve the state at the observation location and advect that improvement towards the Earth, leading to an improvement in forecast skill in near Earth space for both the observed and unobserved variables. However, sharp gradients caused by the analysis of a single observation in space resulted in artificial wave-like structures being advected towards Earth. This paper is the first attempt to apply DA to solar wind prediction, and provides the first in-depth analysis of the challenges and potential solutions