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1.
Age Ageing ; 49(3): 481-486, 2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-32040192

RESUMO

INTRODUCTION: The impact and outcome of hip fractures are well described for people living in the community, but inpatient hip fracture (IHF) have not been extensively studied. In this study, we examine the patient characteristics, common falls risk factors and clinical outcomes of this condition. METHODS: Between January 2016 and December 2017, we analysed all inpatient falls that resulted in hip fracture within Aneurin Bevan University Health Board (ABUHB) in Wales. RESULTS: The overall falls rate was 8.7/1000 occupied bed days (OBD). Over the 2 years, 118 patients sustained an IHF, giving a rate of 0.12/1000 OBD. The mean age was 81.8 ± 9.5 (range 49-97) years and 60% were women. Most patients (n = 112) were admitted from their own home. Mean Charlson Comorbidity Index and the number of medications on admission were 5.5 ± 1.9 and 8.5 ± 3.7, respectively.Fifty-three patients (45%) sustained the IHF following their first inpatient fall. Twenty-four IHF (20%) occurred within 72 h. Mean length of stay was 84.9 ± 55.8 days. Only 43% were discharged back to their original place of residence following an IHF; 27% were discharged to a care home (26 new care home discharges), and 30% died as an inpatient. One-year mortality was 54% (n = 64/118). The most common comorbidity was dementia (63%). CONCLUSION: Mortality and need for care home placement are both much higher after IHF than following community hip fracture. Most people who suffer a hip fracture in hospital have already demonstrated their need for falls risk management by having fallen previously during the same admission.


Assuntos
Fraturas do Quadril , Pacientes Internados , Acidentes por Quedas , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Quadril/diagnóstico , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/terapia , Hospitalização , Humanos , País de Gales/epidemiologia
2.
Age Ageing ; 44(6): 1032-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26399649

RESUMO

BACKGROUND: Falls in hospital account for almost two-fifths of the patient safety incidents reported to the National Reporting and Learning System in U.K. Studies have suggested an increased incidence of falls in single-bedded hospitals. OBJECTIVE: To compare the outcome of in-patient falls occurring in units with 100% single rooms (SRs) and multi-bedded wards (M-BWs). SAMPLING DESIGN AND METHODS: An observational study. Retrospective standard incident reporting data (DATIX) on in-patient falls and associated injury were obtained from both sites over 18 months each. There was no change in demographics, size and characteristics of population except change in the geography of new hospitals. RESULTS: The total number of in-patient fall incidents reported over the 3 years was 1,749. The mean age of patients on M-BW and SR sites was 81.0 ± 2.4 (51.3% females) and 80.3 ± 10.3 (50.7% females), respectively. The mean incidence of falls/1,000 patient-bed days on M-BW and SR sites was 5.44 ± 4.76 and 15.82 ± 19.56, respectively (P < 0.01). Overall fracture incidence/1,000 patient-bed days on M-BW and SR sites was 0.07 ± 0.48 and 0.36 ± 1.52 (P < 0.01), respectively. The hip fracture incidence/1,000 patient-bed days on M-BW and SR sites was 0.04 ± 0.38 and 0.15 ± 1.00 (P < 0.01), respectively. One-year mortality from the date of first incident fall was lower in M-BWs (41.1%) compared with SRs (47.1%), but this is not significant (P = 0.12). CONCLUSION: This observational study shows a significantly increased incidence of falls and fracture in a hospital design with SRs compared with a multi-bedded facility. Consideration should be given to increased incidence of falls and falls-related injury in SRs when deciding on the percentage of single-room provision in new hospitals to admit frail older adults.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Pacientes Internados/estatística & dados numéricos , Quartos de Pacientes/estatística & dados numéricos , Idoso de 80 Anos ou mais , Feminino , Ambiente de Instituições de Saúde/estatística & dados numéricos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Reino Unido/epidemiologia
3.
AIDS Res Hum Retroviruses ; 39(2): 76-83, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36424832

RESUMO

Microsporidiosis caused by Enterocytozoon bieneusi is a common opportunistic infection in patients with HIV/AIDS and those on immunosuppressive therapy. A significant loss of mucosal or peripheral CD4+ T cells and subsequent dysfunction of the intestinal immune system may be responsible for the development of chronic microsporidiosis in these patients. We have used the Simian immunodeficiency virus (SIV)-infected macaque model to investigate this relationship. To establish the course of E. bieneusi infection in SIV-infected animals, four SIV-infected animals were experimentally challenged with E. bieneusi when their CD4+ counts dropped to less than 300 cells/µL of blood. Analysis of fecal samples by nested polymerase chain reaction revealed that three out of four E. bieneusi-infected macaques continued to shed spores for 7-24 months after infection, an indication of chronic microsporidiosis. Four other SIV-infected macaques, after having an initial negative phase, spontaneously acquired E. bieneusi infection when their CD4+ counts dropped to less than 600 cells/µL of blood and shed spores for 8-19 months. The shedding of E. bieneusi spores in the feces increased relative to decrease in peripheral blood CD4+ T cell numbers. Gut biopsies were obtained before and after challenge to phenotype the mucosal lymphocyte subsets using flow cytometry. The immunophenotypic analysis showed no restoration of CD4+ T cells after E. bieneusi infection in the intestinal cells. A slight increase in the percentage population of CD4+ T cells in peripheral blood did not have any effect on the control of E. bieneusi infection in the SIV-infected macaques. These preliminary studies demonstrate that SIV-infected macaques develop chronic E. bieneusi infections as their CD4+ counts dropped to below 300 cells/µL of blood.


Assuntos
Enterocytozoon , Infecções por HIV , Microsporidiose , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Animais , Síndrome de Imunodeficiência Adquirida dos Símios/complicações , Macaca mulatta , Microsporidiose/patologia , Linfócitos T CD4-Positivos
4.
Cureus ; 15(3): e36532, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37102000

RESUMO

Leukocytoclastic vasculitis (LCV) is a cutaneous small vessel vasculitis that is characterized by the development of a non-blanching palpable purpura. Diagnosis is made by skin biopsy and histopathology which shows subepidermal acantholysis with dense neutrophilic infiltrate leading to fibrinoid necrosis of the dermal blood vessels. Etiology is generally idiopathic in most cases but secondary causes include chronic infections, malignancies, systemic autoimmune conditions, and medication use. Treatment involves supportive measures in the case of idiopathic LCV, and treatment of the offending condition or agent in LCV due to a secondary cause. A 59-year-old male presented with purulent ulcers on the plantar surface of the right foot. Radiograph of the right foot showed soft tissue swelling without evidence of osteomyelitis. Empiric antibiotic treatment with vancomycin was initiated. A wound culture was obtained from the purulent drainage which grew positive for methicillin-resistant Staphylococcus aureus (MRSA). On the fourth day of treatment with vancomycin, multiple symmetric, purpuric lesions arose on the patient's trunk and extremities. Skin biopsy with histopathology showed subepidermal acantholysis with neutrophil-predominant inflammatory infiltrate consistent with leukocytoclastic vasculitis. Vancomycin was discontinued and the patient's exanthem began to regress, with full resolution after 30 days post withdrawal of the antibiotic.

5.
Cureus ; 15(6): e40082, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37425600

RESUMO

Subclavian artery pseudoaneurysm (PSA) is a rare complication arising from transaxillary Impella device placement during high-risk percutaneous coronary intervention (PCI). Despite the increasing prevalence of Impella use, literature addressing this complication is scarce. This case emphasizes the limited existing evidence on subclavian artery PSA and highlights the importance of recognizing it as a potential risk. With high-risk PCI and Impella use gaining popularity, understanding this complication is crucial for early detection and appropriate management. A 62-year-old male with a past medical history of type II diabetes mellitus, peripheral artery disease, hypertension, and chronic tobacco use presents with recurrent episodes of exertional chest pain and dyspnea. Initial workup with an electrocardiogram showed ST-segment elevations in the anteroseptal leads. The patient underwent right- and left-sided cardiac catheterization, which revealed severe stenosis of the left anterior descending artery and findings of cardiogenic shock. The patient required mechanical circulatory support with a percutaneous left ventricular assist device during the procedure; this was placed via transaxillary approach due to the patient having peripheral artery disease in bilateral femoral arteries. The patient had a complicated clinical course, but the patient's clinical picture slowly improved, and the percutaneous left ventricular assist device was removed. Roughly six weeks after the removal of the device, the patient developed a large fluid collection in the chest wall anterior to the left shoulder. Imaging revealed a ruptured left distal subclavian artery PSA. The patient was promptly taken to the catheterization laboratory and a covered stent was deployed over the site of the PSA. Repeat angiography revealed brisk flow through the left subclavian artery into the axillary artery with no extravasation into the chest wall.

6.
Cureus ; 15(6): e41039, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37519530

RESUMO

Pylephlebitis is a rare complication of intra-abdominal infections and has a significant mortality rate, necessitating early recognition for optimal treatment. Here, we present the case of a 36-year-old male with fever, shortness of breath, cough, and epigastric pain. He was ultimately diagnosed with hepatic vein pylephlebitis along with multiple pulmonary and hepatic lesions believed to be septic emboli and hepatic abscess. He developed recurrent bilateral pyopneumothorax which required drainage by interventional radiology multiple times. The patient improved and was discharged on intravenous antibiotics for four weeks. While hepatic abscesses are a known complication of pylephlebitis, pyopneumothorax is a rare, unreported complication. Recognition of this potential complication is important for clinicians when treating patients with hepatic vein pylephlebitis.

7.
Cureus ; 15(3): e36455, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37090411

RESUMO

As dipeptidyl peptidase-4 inhibitors are becoming more utilized in the treatment of diabetes, it is important to recognize their side effects and become more familiar with them. As these side effects arise, physicians are more prepared to recognize and discontinue these medications. This case report describes a 34-year-old male who initially presented with a hemoglobin A1c greater than 16%. After titration of his diabetic medications, he presented with pancreatitis diagnosed by symptoms and imaging. Common causes of pancreatitis were ruled out, including biliary pathology, alcohol use, tobacco use, elevated calcium levels, and hypertriglyceridemia. The patient followed up in the clinic with persistent symptoms. A review of his medication list revealed pancreatitis as a side effect of linagliptin. After holding this medication, his symptoms improved over the course of a month.

8.
Cureus ; 15(3): e36695, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37113373

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) and coronavirus disease 2019 (COVID-19) predominantly cause respiratory symptoms but cardiovascular complications from COVID-19 have been documented in the literature. Acute pericarditis has been known to be caused by COVID-19 but severe cardiac complications, such as cardiac tamponade, have rarely been reported. Early diagnosis and treatment with pericardiocentesis are imperative, as this can improve patient outcomes. A 56-year-old female presented with chest pain and recurrent episodes of presyncope. The patient tested positive for SARS-Cov-2 through a polymerase chain reaction (PCR) test. The patient was hypotensive on arrival and the initial workup with electrocardiogram was significant for sinus tachycardia with low voltage QRS complexes in the precordial and limb leads. A transthoracic echocardiogram was also done and showed a large circumferential pericardial effusion with chamber collapse of the right atrium and right ventricle during diastole indicative of tamponade physiology. The patient's clinical course was complicated by pulseless electrical activity cardiac arrest during which a pericardiocentesis was done. One hundred (100) mL of serous pericardial fluid was drained and a return of spontaneous circulation was obtained after roughly 10 minutes of cardiopulmonary resuscitation. Further infectious and noninfectious workups, including malignant and rheumatologic etiologies for acute pericarditis, were negative. The patient was subsequently treated with high-dose non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine for viral pericarditis. The patient's clinical course improved, and the patient was subsequently discharged after a prolonged hospital course to a subacute rehabilitation facility to undergo physical therapy.

9.
Cureus ; 15(3): e35895, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37033585

RESUMO

Dilated cardiomyopathy (DCM) is a myocardial disease that is characterized by left ventricular or biventricular dilation and impairment of systolic function. The etiology is often unknown although it has been thought that DCM may be a consequence of viral myocarditis. The most commonly implicated viruses in the development of myocarditis include coxsackie B virus, hepatitis, parvovirus, cytomegalovirus, influenza virus, and adenovirus. DCM carries a poor prognosis and high rates of mortality, therefore early diagnosis and treatment are imperative. A 47-year-old male presented with atypical chest pain, along with progressive dyspnea. The patient also endorsed symptoms consistent with acute viral syndrome roughly one week prior to presenting to the hospital. The patient initially presented in cardiogenic shock. An initial workup including an echocardiogram was done and showed an ejection fraction of 10-15% with severe left ventricular and left atrial dilation. Left-sided cardiac catheterization revealed nonobstructive coronary artery disease. The patient was placed on mechanical circulatory and inotropic support and was transferred to the cardiovascular intensive care unit. Cardiac MRI was done and showed a moderately sized pericardial effusion along with signs indicative of myocarditis. Serologic testing was positive for coxsackie B virus type IV antibodies. The patient's clinical picture improved as circulatory and inotropic support was removed and the patient was discharged with close outpatient follow-up and evaluation for cardiac transplant.

10.
Cureus ; 15(5): e38699, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37292540

RESUMO

Nutritional support is essential for critically ill patients to reduce mortality and length of stay. Frequently nasogastric (NG) tubes are used to provide enteral nutrition. A very rare risk of NG tube placement is esophageal perforation, most commonly in the thoracic portion of the esophagus. Here we describe a case of a 41-year-old male with multiple risk factors for esophageal integrity disruption who initially presented for diabetic ketoacidosis (DKA) requiring intubation. Following intubation, an NG tube was placed for nutritional support. The following day the patient developed hydropneumothorax and hydropneumoperitoneum. He was taken emergently for surgical correction of suspected perforation. It was found that the patient had esophageal perforation from the distal esophagus to the proximal portion of the lesser curvature of the stomach. The NG tube transversed the proximal portion of the tear and re-entered at a distal site. The distal portions of the esophagus showed necrotic superficial layers with viable muscularis layers. The patient gradually improved after surgical intervention and was discharged to a long-term acute care facility. It is essential as medical providers to be familiar with complications of NG tube placement and risk factors that could increase the risk of esophageal perforation.

11.
Sci Rep ; 13(1): 9379, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-37296129

RESUMO

The present investigation aimed to identify genome wide SNPs and to carry out diversity and population structure study using ddRAD-seq based genotyping of 58 individuals of six indigenous milch cattle breeds (Bos indicus) such as Sahiwal, Gir, Rathi, Tharparkar, Red Sindhi and Kankrej of India. A high percentage of reads (94.53%) were mapped to the Bos taurus (ARS-UCD1.2) reference genome assembly. Following filtration criteria, a total of 84,027 high quality SNPs were identified across the genome of 6 cattle breeds with the highest number of SNPs observed in Gir (34,743), followed by Red Sindhi (13,092), Kankrej (12,812), Sahiwal (8956), Tharparkar (7356) and Rathi (7068). Most of these SNPs were distributed in the intronic regions (53.87%) followed by intergenic regions (34.94%) while only 1.23% were located in the exonic regions. Together with analysis of nucleotide diversity (π = 0.373), Tajima's D (D value ranging from - 0.295 to 0.214), observed heterozygosity (HO ranging from 0.464 to 0.551), inbreeding coefficient (FIS ranging from - 0.253 to 0.0513) suggested for the presence of sufficient within breed diversity in the 6 major milch breeds of India. The phylogenetic based structuring, principal component and admixture analysis revealed genetic distinctness as well as purity of almost all of the 6 cattle breeds. Overall, our strategy has successfully identified thousands of high-quality genome wide SNPs that will further enrich the Bos indicus representation basic information about genetic diversity and structure of 6 major Indian milch cattle breeds which should have implications for better management and conservation of valuable indicine cattle diversity.


Assuntos
Genoma , Polimorfismo de Nucleotídeo Único , Bovinos/genética , Animais , Genótipo , Filogenia , Endogamia , Índia
12.
AAPS J ; 25(4): 55, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37266912

RESUMO

A survey conducted by the Therapeutic Product Immunogenicity (TPI) community within the American Association of Pharmaceutical Scientists (AAPS) posed questions to the participants on their immunogenicity risk assessment strategies prior to clinical development. The survey was conducted in 2 phases spanning 5 years, and queried information about in silico algorithms and in vitro assay formats for immunogenicity risk assessments and how the data were used to inform early developability effort in discovery, chemistry, manufacturing and control (CMC), and non-clinical stages of development. The key findings representing the trends from a majority of the participants included the use of high throughput in silico algorithms, human immune cell-based assays, and proteomics based outputs, as well as specialized assays when therapeutic mechanism of action could impact risk assessment. Additional insights into the CMC-related risks could also be gathered with the same tools to inform future process development and de-risk critical quality attributes with uncertain and unknown risks. The use of the outputs beyond supporting early development activities was also noted with participants utilizing the risk assessments to drive their clinical strategy and streamline bioanalysis.


Assuntos
Desenvolvimento de Medicamentos , Humanos , Consenso , Medição de Risco/métodos
13.
Age Ageing ; 41(2): 242-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22301571

RESUMO

BACKGROUND: multidisciplinary rehabilitation is of proven benefit in the management of older inpatients. However, the identification of patients who will do well with rehabilitation currently lacks a strong evidence base. OBJECTIVES: the aims of this study were to compare the importance of chronological age, gender, co-morbidities and frailty in the prediction of adverse outcomes for patients admitted to an acute geriatric rehabilitation ward. DESIGN: prospective observational cohort study. SUBJECTS AND SETTING: two hundred and sixty-five patients admitted consecutively to an acute geriatric rehabilitation ward at a tertiary care teaching hospital. METHODS: frailty status was measured by an index of accumulated deficits, giving a potential score from 0 (no deficits) to 1.0 (all 40 deficits present). Patients were stratified into three outcomes: good (discharged to original residence within 28 days), intermediate (discharged to original residence but longer hospital stay) and poor (newly institutionalised or died). RESULTS: patients were old (82.6 ± 8.6 years) and frail (mean frailty index (FI) 0.34 ± 0.09). Frailty status correlated significantly with length of stay and was a predictor of poor functional gain. The odds ratio of intermediate and poor outcome relative to a good outcome was 4.95 (95% CI = 3.21, 7.59; P < 0.001) per unit increase in FI. Chronological age, gender and co-morbidity showed no significant association with outcomes. CONCLUSION: frailty is associated with adverse rehabilitation outcomes. The FI may have clinical utility, augmenting clinical judgement in the management of older inpatients.


Assuntos
Geriatria , Unidades Hospitalares , Institucionalização , Equipe de Assistência ao Paciente , Alta do Paciente , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Comorbidade , Feminino , Idoso Fragilizado , Avaliação Geriátrica , Geriatria/estatística & dados numéricos , Indicadores Básicos de Saúde , Mortalidade Hospitalar , Unidades Hospitalares/estatística & dados numéricos , Hospitais de Ensino , Humanos , Institucionalização/estatística & dados numéricos , Estimativa de Kaplan-Meier , Tempo de Internação , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Alta do Paciente/estatística & dados numéricos , Seleção de Pacientes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento , País de Gales
14.
J Cancer Res Ther ; 18(1): 119-123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35381772

RESUMO

Background: Cancers in the head-and-neck region are the sixth most common cancers worldwide with an increasing incidence in developing countries. Methods: This study was carried out in the department of ENT and head-and-neck surgery in collaboration with the department of radiotherapy for a period of 1 year extending from May 01, 2014, to April 30, 2015. A total of 48 cases of metastatic secondary nodes were included in the study. Results: The male-to-female ratio in the present study was 4.33:1. Maximum number of patients were seen in the seventh decade. The youngest patient was a female 30 years old and the oldest was a male of 80 years. About 95.84% of primary tumors were squamous cell carcinomas and 40.47% of the patients of head-and-neck cancer with metastatic lymph nodes had well-differentiated squamous cell carcinomas. Majority of cases presented with N2 nodes, while N1 nodes were highest in cases of carcinomas larynx. Conclusions: Metastatic neck disease is a major problem in patients with head-and-neck cancer. The therapeutic goal includes not only known disease but also the elimination of possible subclinical disease. The judicious use of moderate doses of irradiation and modified surgical procedures should be used in specific clinical situations to significantly decrease neck recurrences while eliminating morbidity.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Adulto , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Masculino , Pescoço/patologia , Estadiamento de Neoplasias
15.
Cureus ; 14(7): e26616, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35936142

RESUMO

Fournier's gangrene (FG) is necrotizing fasciitis that affects the penis, scrotum, or perineum. Males are more likely to get affected by this disease. The most common predisposing risk factors are diabetes, alcoholism, hypertension, smoking, and immunosuppressive disorders. FG is a polymicrobial infection caused by both aerobic and anaerobic bacteria. The most common aerobic organisms are Escherichia coli, Klebsiella, Proteus, Staphylococcus, and Streptococcus. The most common anaerobic organisms are Bacteroides, Clostridium, and Peptostreptococcus. The disease carries high mortality and morbidity, so timely diagnosis and treatment are of utmost importance. Here, we report a case of a 61-year-old male with a medical history significant for benign prostatic hyperplasia (BPH), who presented to our hospital with fever, watery diarrhea, and painful swelling of the scrotum and penis. The patient was started on piperacillin-tazobactam, vancomycin, and clindamycin. A computed tomography scan of the pelvis showed prostatic enlargement, edema of the penis and scrotum, and air collection within the corpus cavernosum. The patient underwent multiple surgical debridements of the glans penis. Patient wound cultures were positive for Streptococcus anginosus, Actinomyces turicensis, and Peptoniphilus harei. As mentioned earlier, FG is common in diabetic and immunocompromised patients, and infection is usually polymicrobial. Our patient was immunocompetent and his cultures grew atypical organisms.

16.
Front Immunol ; 13: 999021, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189251

RESUMO

AAV gene transfer is a promising treatment for many patients with life-threatening genetic diseases. However, host immune response to the vector poses a significant challenge for the durability and safety of AAV-mediated gene therapy. Here, we characterize the innate immune response to AAV in human whole blood. We identified neutrophils, monocyte-related dendritic cells, and monocytes as the most prevalent cell subsets able to internalize AAV particles, while conventional dendritic cells were the most activated in terms of the CD86 co-stimulatory molecule upregulation. Although low titers (≤1:10) of AAV neutralizing antibodies (NAb) in blood did not have profound effects on the innate immune response to AAV, higher NAb titers (≥1:100) significantly increased pro-inflammatory cytokine/chemokine secretion, vector uptake by antigen presenting cells (APCs) and complement activation. Interestingly, both full and empty viral particles were equally potent in inducing complement activation and cytokine secretion. By using a compstatin-based C3 and C3b inhibitor, APL-9, we demonstrated that complement pathway inhibition lowered CD86 levels on APCs, AAV uptake, and cytokine/chemokine secretion in response to AAV. Together these results suggest that the pre-existing humoral immunity to AAV may contribute to trigger adverse immune responses observed in AAV-based gene therapy, and that blockade of complement pathway may warrant further investigation as a potential strategy for decreasing immunogenicity of AAV-based therapeutics.


Assuntos
Dependovirus , Vetores Genéticos , Anticorpos Neutralizantes , Citocinas/genética , Dependovirus/genética , Vetores Genéticos/genética , Humanos , Imunidade Humoral
17.
Indian Dermatol Online J ; 12(5): 683-686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34667753

RESUMO

Case report is regarded as one of the first line of evidence in medical science. There have been numerous circumstances, where the initial dissemination (and breakthrough) of scientific knowledge had been done, with the help of case reports. Case report is a particular variety of manuscript that showcases the unusual features and management of a patient. The words of William Osler (Father of modern medicine) "Always note and record the unusual…publish it. Place it on permanent record as a short, concise note. Such communications are always of value," still hold relevance in today's era. In this article, we shall discuss the keys to draft a case report worthy of publication.

18.
Front Genet ; 12: 641925, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34113375

RESUMO

Non-syndromic hearing loss (NSHL) is one of the most frequent auditory deficits in humans characterized by high clinical and genetic heterogeneity. Very few studies have reported the relationship between OTOF (Locus: DFNB9) and hereditary hearing loss in India. We aimed to decipher the genetic cause of prelingual NSHL in a large affected Muslim consanguineous families using whole-exome sequencing (WES). The study was performed following the guidelines and regulations of the Indian Council of Medical Research (ICMR), New Delhi. The population was identified from Jammu and Kashmir, the Northernmost part of India. Near about 100 individuals were born deaf-mute in the village of 3,000 inhabitants. A total of 103 individuals (with 52 cases and 51 controls) agreed to participate in this study. Our study revealed a rare non-sense homozygous mutation NC_000002.11:g.2:26702224G>A; NM_001287489.2:c.2122C>T; NP_001274418.1:p.(Arg708∗) in the 18th exon of the OTOF gene. Our study provides the first insight into this homozygous condition, which has not been previously reported in ExAC, 1,000 Genome and genomAD databases. Furthermore, the variant was confirmed in the population cohort (n = 103) using Sanger sequencing. In addition to the pathogenic OTOF variant, the WES data also revealed novel and recurrent mutations in CDH23, GJB2, MYO15A, OTOG, and SLC26A4 genes. The rare pathogenic and the novel variants observed in this study have been submitted to the ClinVar database and are publicly available online with the accessions SCV001448680.1, SCV001448682.1 and SCV001448681.1. We conclude that OTOF-related NSHL hearing loss is prevalent in the region due to successive inbreeding in its generations. We recommend premarital genetic testing and genetic counseling strategies to minimize and control the disease risk in future generations.

19.
Geriatrics (Basel) ; 5(4)2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33266236

RESUMO

Introduction: dementia increases the risk of falls by 2-3 times and cognitively impaired patients are three times more likely to have hip fracture following a fall when compared to cognitively intact individuals. However, there is not enough evidence that explores the relationship between dementia and fragility fractures. The aim of this study is to explore the relationships of prevalent fragility fracture in patients with dementia admitted with an acute illness to the hospital. Methods: the existing Health Board records were reviewed retrospectively for all patients admitted diagnosed with dementia in the year 2016. All patients were followed up for a maximum of three years. All of the the dementia patients were divided into three groups: group 1-"no fractures"; group 2-"all fractures"; group 3-"fragility fractures". Clinical outcomes were analysed for hospital stay, discharge destination (new care home), post-discharge hip fracture data, and mortality. Results: dementia patients with a prevalent fracture were significantly older, 62% were women. A significantly higher proportion of dementia patients with prevalent fractures were care home residents and taking a significantly higher number of medications. The mean Charlson comorbidity index was similar in patients with or without fracture. Dementia patients with a prevalent fracture required a new care home and this is significantly higher when compared to those with no fracture. Mortality at one year and three year was not statistically different in patients with or without prevalent fractures. A significantly higher number (21.5%) of dementia patients with prevalent fragility fracture sustained a new hip fracture when compared to those with no prevalent osteoporotic fracture (2.9%) over the three years follow up (p < 0.0001). Conclusion: dementia patients with a prevalent fragility fracture is associated with a statistically significant higher risk of a new care home placement following acute hospital admission. This sub-group is also at risk of a new hip fracture in the next three years. Whilst clinical judgement remains crucial in the care of frail older people, it is prudent to consider medical management of osteoporosis in dementia if deemed to be beneficial following the comprehensive geriatric assessment.

20.
Altern Lab Anim ; 37 Suppl 1: 19-27, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19807200

RESUMO

While the duration and size of human clinical trials may be difficult to reduce, there are several parameters in pre-clinical vaccine development that may be possible to further optimise. By increasing the accuracy of the models used for pre-clinical vaccine testing, it should be possible to increase the probability that any particular vaccine candidate will be successful in human trials. In addition, an improved model will allow the collection of increasingly more-informative data in pre-clinical tests, thus aiding the rational design and formulation of candidates entered into clinical evaluation. An acceleration and increase in sophistication of pre-clinical vaccine development will thus require the advent of more physiologically-accurate models of the human immune system, coupled with substantial advances in the mechanistic understanding of vaccine efficacy, achieved by using this model. We believe the best viable option available is to use human cells and/or tissues in a functional in vitro model of human physiology. Not only will this more accurately model human diseases, it will also eliminate any ethical, moral and scientific issues involved with use of live humans and animals. An in vitro model, termed "MIMIC" (Modular IMmune In vitro Construct), was designed and developed to reflect the human immune system in a well-based format. The MIMIC System is a laboratory-based methodology that replicates the human immune system response. It is highly automated, and can be used to simulate a clinical trial for a diverse population, without putting human subjects at risk. The MIMIC System uses the circulating immune cells of individual donors to recapitulate each individual human immune response by maintaining the autonomy of the donor. Thus, an in vitro test system has been created that is functionally equivalent to the donor's own immune system and is designed to respond in a similar manner to the in vivo response.


Assuntos
Alternativas aos Testes com Animais , Endotélio Vascular/imunologia , Leucócitos/imunologia , Tecido Linfoide/imunologia , Modelos Imunológicos , Vacinas/imunologia , Animais , Anticorpos Antibacterianos/biossíntese , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/imunologia , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Ensaios de Triagem em Larga Escala , Humanos , Toxina Tetânica/administração & dosagem , Toxina Tetânica/imunologia
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