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1.
Nature ; 628(8009): 835-843, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38600381

RESUMEN

Severe influenza A virus (IAV) infections can result in hyper-inflammation, lung injury and acute respiratory distress syndrome1-5 (ARDS), for which there are no effective pharmacological therapies. Necroptosis is an attractive entry point for therapeutic intervention in ARDS and related inflammatory conditions because it drives pathogenic lung inflammation and lethality during severe IAV infection6-8 and can potentially be targeted by receptor interacting protein kinase 3 (RIPK3) inhibitors. Here we show that a newly developed RIPK3 inhibitor, UH15-38, potently and selectively blocked IAV-triggered necroptosis in alveolar epithelial cells in vivo. UH15-38 ameliorated lung inflammation and prevented mortality following infection with laboratory-adapted and pandemic strains of IAV, without compromising antiviral adaptive immune responses or impeding viral clearance. UH15-38 displayed robust therapeutic efficacy even when administered late in the course of infection, suggesting that RIPK3 blockade may provide clinical benefit in patients with IAV-driven ARDS and other hyper-inflammatory pathologies.


Asunto(s)
Lesión Pulmonar , Necroptosis , Infecciones por Orthomyxoviridae , Inhibidores de Proteínas Quinasas , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Animales , Femenino , Humanos , Masculino , Ratones , Células Epiteliales Alveolares/patología , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/virología , Células Epiteliales Alveolares/metabolismo , Virus de la Influenza A/clasificación , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/inmunología , Virus de la Influenza A/patogenicidad , Lesión Pulmonar/complicaciones , Lesión Pulmonar/patología , Lesión Pulmonar/prevención & control , Lesión Pulmonar/virología , Ratones Endogámicos C57BL , Necroptosis/efectos de los fármacos , Infecciones por Orthomyxoviridae/complicaciones , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/mortalidad , Infecciones por Orthomyxoviridae/virología , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/antagonistas & inhibidores , Síndrome de Dificultad Respiratoria/complicaciones , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/prevención & control , Síndrome de Dificultad Respiratoria/virología
2.
Int J Mol Sci ; 22(20)2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34681611

RESUMEN

The herbal plant Angelica gigas (A. gigas) has been used in traditional medicine in East Asian countries, and its chemical components are reported to have many pharmacological effects. In this study, we showed that a bioactive ingredient of A. gigas modulates the functional activity of macrophages and investigated its effect on inflammation using a sepsis model. Among 12 different compounds derived from A. gigas, decursinol angelate (DA) was identified as the most effective in suppressing the induction of TNF-α and IL-6 in murine macrophages. When mice were infected with a lethal dose of methicillin-resistant Staphylococcus aureus (MRSA), DA treatment improved the mortality and bacteremia, and attenuated the cytokine storm, which was associated with decreased CD38+ macrophage populations in the blood and liver. In vitro studies revealed that DA inhibited the functional activation of macrophages in the expression of pro-inflammatory mediators in response to microbial infection, while promoting the bacterial killing ability with an increased production of reactive oxygen species. Mechanistically, DA treatment attenuated the NF-κB and Akt signaling pathways. Intriguingly, ectopic expression of an active mutant of IKK2 released the inhibition of TNF-α production by the DA treatment, whereas the inhibition of Akt resulted in enhanced ROS production. Taken together, our experimental evidence demonstrated that DA modulates the functional activities of pro-inflammatory macrophages and that DA could be a potential therapeutic agent in the management of sepsis.


Asunto(s)
Benzopiranos/farmacología , Butiratos/farmacología , Macrófagos/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Sepsis/patología , Angelica/química , Angelica/metabolismo , Animales , Benzopiranos/química , Butiratos/química , Modelos Animales de Enfermedad , Interleucina-6/metabolismo , Estimación de Kaplan-Meier , Lipopolisacáridos/farmacología , Macrófagos/citología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Sepsis/microbiología , Sepsis/mortalidad , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo
3.
BMC Psychiatry ; 20(1): 491, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-33023563

RESUMEN

BACKGROUND: COVID-19 pandemic has created unprecedented health and economic impact. Psychological stress, anxiety and depression are affecting not only COVID-19 patients but also health professionals, and general population. Fear of contracting COVID-19, forced restrictive social measures, and economic hardship are causing mental trauma. Nepal is a developing country from South Asia where the COVID-19 pandemic is still evolving. This online survey has been carried out to understand impact of COVID- 19 on mental health of Nepalese community dwellers. METHODS: The COVID-19 Peritraumatic Distress Index (CPDI) questionnaire adapted from the Shanghai Mental Health Centre was used for online data collection from 11 April-17 May 2020. Collected data were extracted to Microsoft excel-13 and imported and analyzed using SPSS (Statistical Package for Social Sciences) version-22. An initial univariate analysis was conducted for all variables to assess the distribution. Logistic regression analyses were done to estimate the odds ratios of relevant predicting variables. RESULTS: A total of 410 participants completed the self-rated questionnaires. Mean age of study participants was 34.8 ± 11.7 years with male preponderance. 88.5% of the respondents were not in distress (score less than 28) while, 11% had mild to moderate distress and 0.5% had severe distress. The prevalence of distress is higher among age group > 45 years, female gender, and post-secondary education group. Health professional were more likely to get distressed. Respondents with post-secondary education had higher odds (OR = 3.32; p = 0.020) of developing distress as compared to respondents with secondary education or lower. CONCLUSION: There is lower rate of psychological distress in city dwellers and people with low education. Adequate intervention and evaluation into mental health awareness, and psychosocial support focused primarily on health care workers, female and elderly individuals is necessary.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Distrés Psicológico , Estrés Psicológico/epidemiología , Adulto , COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nepal/epidemiología , Prevalencia , SARS-CoV-2 , Factores Socioeconómicos , Estrés Psicológico/psicología , Encuestas y Cuestionarios
4.
Biochem Biophys Res Commun ; 450(4): 1696-701, 2014 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-25063025

RESUMEN

Tumor-infiltrating macrophages are potential candidates for cancer immunotherapy. However, the detailed molecular mechanism underlying macrophage infiltration into tumors is poorly understood. Based on our previous finding that plasminogen activator inhibitor-1 (PAI-1) enhances vitronectin-dependent migration of macrophages, we investigated the potential role of PAI-1 in macrophage invasion into melanoma. Experimental evidence obtained from spheroid confrontation assay clearly showed that PAI-1 overexpression significantly enhanced the invasion of RAW 264.7 cells into B16F10 melanoma. We further demonstrated that PAI-1 induces phosphorylation of focal adhesion kinase (FAK) at Tyr(925), which, in turn, mediated the invasion of macrophages into the melanoma. This work further illustrates that low-density lipoprotein receptor related-protein 1 (LRP1) is essential for PAI-1-mediated FAK phosphorylation and macrophage invasion into melanoma. In conclusion, our study demonstrates a novel role of PAI-1 in macrophage invasion into melanoma and provides insights into the underlying molecular mechanism.


Asunto(s)
Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Macrófagos/patología , Melanoma Experimental/patología , Inhibidor 1 de Activador Plasminogénico/fisiología , Tirosina/metabolismo , Animales , Secuencia de Bases , Línea Celular , Cartilla de ADN , Proteína-Tirosina Quinasas de Adhesión Focal/química , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad , Melanoma Experimental/enzimología , Ratones , Fosforilación , Receptores de LDL/metabolismo , Proteínas Supresoras de Tumor/metabolismo
5.
Ann Med Surg (Lond) ; 86(4): 2352-2356, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38576951

RESUMEN

Introduction and importance: Intracranial osteochondroma is rare, presenting diagnostic challenges due to overlapping imaging findings with other pathologies. This case report highlights the significance of considering osteochondroma in calcified tumour differentials near bone. Case presentation: A 34-year-old man with vision deterioration and headaches had an MRI revealing a suprasellar lesion. Intraoperatively, a bony hard tumour was partially resected. Subsequent computed tomography (CT) confirmed a calcified mass contiguous with the posterior clinoid. Clinical discussion: Reviewing 28 cases, skull base osteochondromas were common, with differential diagnoses including craniopharyngioma and meningioma. Surgical decision-making involved balancing complete resection for convexity and falx cases versus partial resection for skull base tumours due to proximity to critical structures. Conclusion: Intracranial osteochondroma poses diagnostic challenges, especially near bone. Tailored surgical approaches are vital, with complete resection yielding good outcomes for convexity and falx cases. Close follow-up is crucial for monitoring recurrences and complications.

6.
Ann Med Surg (Lond) ; 86(6): 3249-3254, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38846812

RESUMEN

Background and objective: Benign prostatic hyperplasia manifests as lower urinary tract symptoms (LUTS) and prostate gland enlargement, leading to bladder outlet obstruction with consequent structural and functional impacts on the bladder. Urodynamic studies are resource-intensive and invasive. Detrusor wall thickness (DWT) assessment offers a cost-effective, reproducible alternative for evaluating LUTS severity in males with bladder outlet obstruction, utilizing ultrasonographic examination. Methods: This prospective cross-sectional study, conducted at a tertiary care center from May 2023 to January 2024, included 171 patients with LUTS who underwent transabdominal ultrasound for DWT measurements. LUTS severity, assessed using International Prostate Symptom Scores (IPSS) classified participants into mild and moderate-to-severe symptom groups. Pearson's correlation coefficient assessed the association between DWT and IPSS, and an independent sample t-test compared means, using a significance level of 5% (P-value ≤0.05). Results: This study involved participants aged 65.01±11.55 years with an IPSS score ranging from 1 to 35, with a mean for mild and moderate-to-severe symptom groups were 4±2.12 and 15.93±6.74, respectively. DWT mean of 1.64±0.38 mm for mild, and 2.4±0.43 mm for moderate to severe symptoms. Pearson's correlation (r=0.697, n=171, P<0.001) indicated a strong DWT-LUTS correlation and a significant DWT mean difference between mild and moderate-to-severe symptom groups was found via an independent t-test (P<0.001, 95% CI: -0.8970 to -0.6414). Conclusion: The study establishes the value of transabdominal ultrasound-detected DWT as a cost-effective, noninvasive, and reproducible tool for assessing LUTS severity in males with benign prostatic hyperplasia.

7.
Ann Med Surg (Lond) ; 86(2): 1066-1071, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38333269

RESUMEN

Introduction: The incidence of chronic subdural haematoma (cSDH) is relatively high among the elderly population. Other known risk factors for cSDH include male sex, dependency on anti-platelet or anticoagulant medication, and chronic alcoholism. Although, the standard mode of treatment for cSDH is surgery, embolization of the middle meningeal artery (MMA), either upfront or as an adjunct to surgical evacuation can be used for the treatment of cSDH. Case presentation: The authors present a case of a 75-year-old female with prior history of posterior-lateral wall myocardial infarction (MI) eight years back presented to our centre with the chief complaints of a gradual onset of cough and headache for 2 months. The patient had no history of trauma, loss of consciousness, seizures, and vomiting. There was no history of diabetes, hypertension, pulmonary tuberculosis, and other chronic illness. Discussion: The concurrent use of anti- platelet drug during a surgical procedure can make the treatment challenging. Endovascular treatment can be a primary treatment modality in such situation. Conclusion: Elimination of blood supply by middle meningeal artery embolization is emerging as a safe, minimally invasive alternative to treat cSDH.

8.
JNMA J Nepal Med Assoc ; 61(258): 123-126, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37203977

RESUMEN

Introduction: Spondylolysis can either be asymptomatic or can cause significant low back pain. It is sometimes associated with the translation of one vertebra over another and is termed spondylolisthesis. The aim of the study was to find out the prevalence of spondylolysis among patients without low back pain in a diagnostic centre. Methods: A descriptive cross-sectional study was carried out in a referral diagnostic centre from 15 December 2018 to 14 December 2021 . Ethical approval was obtained from the Nepal Health Research Council (Reference number: 2903). Images of a computed tomography scan of the abdomen performed for other abdominal causes and without low back pain were reconstructed in the sagittal and coronal plane and evaluated for the presence of spondylolysis and spondylolisthesis in the lumbar spine. Demographic data were taken from the hospital records. Convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Results: Among 768 patients without low back pain, spondylolysis was found in 59 (7.68%) (5.80-9.56, 95% Confidence Interval). Spondylolisthesis was found in only 16 (27.1%) individuals with spondylolysis. The majority of spondylolysis cases were encountered in L5 level in 54 (91.53%). The mean age of patients with spondylolysis was 41.9±14.46 years. Male to female ratio was 1:1.18. Conclusions: The prevalence of spondylolysis in our study was found to be similar to other studies done in similar settings. Keywords: low back pain; spondylolisthesis; spondylolysis.


Asunto(s)
Dolor de la Región Lumbar , Espondilolistesis , Espondilólisis , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Espondilolistesis/complicaciones , Espondilolistesis/diagnóstico por imagen , Espondilolistesis/epidemiología , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/epidemiología , Estudios Transversales , Espondilólisis/diagnóstico , Espondilólisis/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Vértebras Lumbares/diagnóstico por imagen
9.
Clin Case Rep ; 11(2): e6925, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36846178

RESUMEN

Urethral duplication is uncommon with few cases reported in the literature. We report a case in which a patient presented with discharge from proximal part of penis since childhood and recent history of infection. The diagnosis of pre-pubic sinus was made and complete excision of the sinus tract was done.

10.
PLoS One ; 18(7): e0288074, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37428760

RESUMEN

BACKGROUND: Informed consent-taking is a part of clinical practice that has ethical and legal aspects attached to it. This protects the autonomy of the patients by providing complete information regarding the rationale, modality, potential risks, benefits, and alternatives of the planned procedure to the patients. This enables the patients to make the right decision for themselves and their care. This study aims to find out if the informed consent-taking process has ensured the active participation of the patients or the next of kin in the decision-making. MATERIALS AND METHODS: This is a prospective cross-sectional study conducted in a military healthcare institution among patients undergoing major surgical procedures from July 2022 to October 2022. Ethical clearance was obtained before the commencement of this study. A structured questionnaire was prepared, and the collected data was refined in Excel and imported into SPSS for analysis. RESULTS: A total of 350 individuals of mean age 47.95 ± 16.057 years were part of this study. The majority of the respondents were married, literate, and family by beneficiary category. All of the respondents received and signed the consent form. About 77% of the respondents read it completely, and 95.4% of them reported that it was understandable. The majority of the patients did not know who was going to perform the surgery, the alternatives to the planned treatment, the benefits of the surgery, or the outcome of non-treatment. On the patient satisfaction scale, 16.28% of the participants agreed that they were satisfied with the informed consent-taking process. CONCLUSION: Deficiencies in the informed consent-taking process were the lack of dissemination of adequate information on the nature, duration, pros and cons, post-operative state, and alternative of the planned procedure. A well-structured format of the consent form that is specific to a particular procedure should be adopted, and various alternatives to it must be disseminated to the patient or the next of kin to improve the quality of the informed consent-taking process.


Asunto(s)
Consentimiento Informado , Humanos , Adulto , Persona de Mediana Edad , Estudios Transversales , Nepal , Estudios Prospectivos , Centros de Atención Terciaria , Encuestas y Cuestionarios
11.
Ann Med Surg (Lond) ; 85(11): 5690-5694, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37915632

RESUMEN

Introduction and importance: A subgaleal abscess is a collection of pus in a potential space between the galea aponeurotica and pericranium. De novo subgaleal abscesses are a subset of subgaleal abscesses that develop in the absence of identifiable risk factors such as head trauma or procedures. However, these have rarely been reported in the literature. Case presentation: We present the case of a 65-year-old woman who presented with a headache for two and a half months, followed by swelling of the right parieto-occipital scalp. She denied any history of trauma, procedures, or anticoagulant use. A diagnosis of subgaleal abscess complicated by osteomyelitis and epidural abscess was made after obtaining a computed tomography of the head. Surgical treatment consisting of drainage, debridement, and craniectomy was performed, and the disease was successfully treated with a 6-week course of antibiotics. Clinical discussion: It is uncommon to have a de novo subgaleal abscess with spontaneous osteomyelitis and an epidural abscess as concurrent complications. The symptoms can be subtle, such as chronic headaches which can lead to delayed hospital visits. Computed tomography of the head is sufficient to make a definitive diagnosis. Appropriate antibiotic therapy and surgical intervention are necessary, which may encompass incision, drainage, debridement, and occasionally a craniectomy in order to achieve full resolution. Conclusions: One should be vigilant when evaluating scalp swelling for possible underlying abscesses. Prompt diagnosis and appropriate surgical treatment with adequate antibiotics are preferred treatment options for de novo subgaleal abscesses.

12.
Front Immunol ; 14: 1165667, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37215126

RESUMEN

Toll-like receptors (TLRs) have a crucial role not only in triggering innate responses against microbes but in orchestrating an appropriate adaptive immunity. However, deregulated activation of TLR signaling leads to chronic inflammatory conditions such as inflammatory bowel disease (IBD). In this study, we evaluated the immunomodulatory potential of a TLR inhibitor in the form of a cell-penetrating peptide using an ulcerative colitis animal model. A peptide derived from the TIR domain of the TLR adaptor molecule TIRAP that was conjugated with a cell-penetrating sequence (cpTLR-i) suppressed the induction of pro-inflammatory cytokines such as TNF-α and IL-1ß in macrophages. In DSS-induced colitis mice, cpTLR-i treatment ameliorated colitis symptoms, colonic tissue damage, and mucosal inflammation. Intriguingly, cpTLR-i attenuated the induction of TNF-α-expressing proinflammatory macrophages while promoting that of regulatory macrophages expressing arginase-1 and reduced type 17 helper T cell (Th17) responses in the inflamed colonic lamina propria. An in vitro study validated that cpTLR-i enhanced the differentiation of monocyte-driven macrophages into mature macrophages with a regulatory phenotype in a microbial TLR ligand-independent manner. Furthermore, the cocultivation of CD4 T cells with macrophages revealed that cpTLR-i suppressed the activation of Th17 cells through the functional modulation of macrophages. Taken together, our data show the immunomodulatory potential of the TLR inhibitor peptide and suggest cpTLR-i as a novel therapeutic candidate for the treatment of IBD.


Asunto(s)
Péptidos de Penetración Celular , Colitis Ulcerosa , Colitis , Enfermedades Inflamatorias del Intestino , Ratones , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Péptidos de Penetración Celular/farmacología , Factor de Necrosis Tumoral alfa , Macrófagos
13.
Ann Med Surg (Lond) ; 85(2): 295-298, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36845804

RESUMEN

Injuries from animal attack are one of the major public health problems at present scenario globally. Proper documentation is required for the study of different types of injuries caused by animal attacks so that early intervention can be done during life-threatening conditions. Case Presentation: A 36-year-old male presented with an alleged history of attack by two rhinoceros sustaining injuries over the abdomen, chest, shoulder and thigh. Clinical Findings and Investigations: There was a lacerated abdomen with evisceration of the stomach, small intestine, transverse colon and omentum and a lacerated wound over the left lateral thigh and left buttock along with the right shoulder. Extended Focused Assessment with Sonography in Trauma ultrasound showed minimal free fluid in the pelvis. Blood profile revealed reduced haemoglobin and deranged prothrombin time/international normalized ratio. Interventions and Outcome: Patient underwent exploratory laparotomy twice with repair of diaphragmatic injury, excision of avulsed greater omentum in the first setting and repair of gastric perforation in the second setting with stable haemodynamic status. Conclusion: Abdominal evisceration injury by rhinoceros attack is life threatening though rare. Its management should consist of assessing for and controlling associated haemorrhage, assessing for bowel content leakage, covering the eviscerated abdominal contents and early reduction of viscera if there is no active bleeding.

14.
J Nepal Health Res Counc ; 20(2): 441-446, 2022 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-36550726

RESUMEN

BACKGROUND: Central sulcus is relatively constant in anatomy and provides an important landmark in lesion localization in high convexity-parasagittal region. The purpose of this study was to evaluate various direct signs of localization of central sulcus in normal axial computed tomography scan of brain. METHODS: This cross-sectional descriptive study was conducted in 377 patients with normal findings in computed tomography scan of brain. Anatomic relationships of high convexity-parasagittal gyri and sulci that form the base for signs used for localization of central sulcus were assessed. The frequency of visualization of each sign was noted. RESULTS: Sigmoid shape "hook" of central sulcus (87%) was the most frequent sign followed by pars bracket sign (85%), thin postcentral gyrus sign (84.5%) and superior frontal sulcus-precentral sulcus sign (81.3%). Most of the central sulcus signs showed significant positive correlations with the increasing age. Pars bracket sign was the second most common sign and did not show correlation with age. CONCLUSIONS: In the absence of anatomic distortion, computed tomography anatomic techniques usually allow identification of the central sulcus on axial section with most useful sign being the sigmoid shape "hook" sign. Application of these signs in combination rather than in isolation helps to identify with near certainty the location of the central sulcus in axial plane.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Humanos , Estudios Transversales , Imagen por Resonancia Magnética/métodos , Nepal , Encéfalo/diagnóstico por imagen , Lóbulo Frontal
15.
PLoS One ; 17(10): e0275722, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36215268

RESUMEN

Influenza is a major cause of highly contagious respiratory illness resulting in high mortality and morbidity worldwide. Annual vaccination is an effective way to prevent infection and complication from constantly mutating influenza strains. Vaccination utilizes preemptive inoculation with live virus, live attenuated virus, inactivated virus, or virus segments for optimal immune activation. The route of administration also affects the efficacy of the vaccination. Here, we evaluated the effects of inoculation with ultraviolet (UV)-inactivated or live influenza A virus strains and compared their effectiveness and cross protection when intraperitoneal and intramuscular routes of administration were used in mice. Intramuscular or intraperitoneal inoculation with UV-inactivated Influenza A/WSN/1933 provided some protection against intranasal challenge with a lethal dose of live Influenza A/WSN/1933 but only when a high dose of the virus was used in the inoculation. By contrast, inoculation with a low dose of live virus via either route provided complete protection against the same intranasal challenge. Intraperitoneal inoculation with live or UV-inactivated Influenza A/Philippines/2/1982 and intramuscular inoculation with UV-inactivated Influenza A/Philippines/2/1982 failed to produce cross-reactive antibodies against Influenza A/WSN/1933. Intramuscular inoculation with live Influenza A/Philippines/2/1982 induced small amounts of cross-reactive antibodies but could not suppress the cytokine storm produced upon intranasal challenge with Influenza A/WSN/1993. None of the tested inoculation conditions provided observable cross protection against intranasal challenge with a different influenza strain. Taken together, vaccination efficacy was affected by the state and dose of the vaccine virus and the route of administration. These results provide practical data for the development of effective vaccines against influenza virus.


Asunto(s)
Vacunas contra la Influenza , Gripe Humana , Infecciones por Orthomyxoviridae , Orthomyxoviridae , Administración Intranasal , Animales , Anticuerpos Antivirales , Modelos Animales de Enfermedad , Humanos , Ratones , Vacunación/métodos , Vacunas de Productos Inactivados
16.
Surg J (N Y) ; 7(1): e3-e10, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33469564

RESUMEN

Background Coronavirus disease 2019 (COVID-19) has evolved as a pandemic of unimaginable magnitude. The health care system is facing a tremendous challenge to provide ethical and quality care. The transformation of the patient-based care to population-based care during the COVID-19 pandemic has raised ethical dilemma among urologists. Our objective is to explore the consensus in modified standard urology care, that can be adopted and applied during COVID-19 and similar pandemic. Methods We adopted an exploratory study design using secondary data. The data were extracted from a web-based medical library using keywords "COVID-19," "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)," and "urology." We identify and extrapolate (screening, eligibility, and inclusion) the data using PRISMA protocol, and summarize pandemic standard urology care under four main themes: (1) general urology care, (2) choice of surgical modality, (3) triage, and (4) urology training. Result We identified 63 academic papers related to our research question. The majority are expert opinions and perspectives on urology care. The common consensus is triage-based urology care and surgeries. Life or organ threatening conditions need immediate attention. Universal protective measures (personal protective equipment, safe operative environment) and protocol-based patient care are necessary to prevent and control SARS-CoV-2 infection. Conservation of the resources and its rational distribution provide an ethical basis for population-based health care during a pandemic. Informed decision making serves best to patients, families, and society during the public health crisis. Conclusion COVID-19 pandemic tends to transform standard urology practice into crisis standard population-based care. The consensus in crisis is drawn from evolving pieces of medical evidence and public health ethics. The provision of urology care during a pandemic is based on the availability of resources; severity of the disease, consequences of deferment of service, and dynamics of the pandemic.

17.
Clin Case Rep ; 9(9): e04798, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34552740

RESUMEN

Hypertriglyceridemia led acute pancreatitis secreted exudative fluid tacked to the right iliac fossa may cause irritation of retroperitoneum leading to acute periappendicular inflammation and acute appendicitis.

18.
J Surg Case Rep ; 2021(6): rjab220, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34104404

RESUMEN

Gastrointestinal stromal tumors (GISTs) occurring outside the gastrointestinal tract are known as extragastrointestinal stromal tumors (EGIST). They share some common histopathologic and molecular characteristics. This report describes two female patients who were suspected of having a mesenteric GIST, but opted for surveillance rather than definitive treatment. Upon reassessment, both patients demonstrated increased tumor mass with no evidence of distant metastasis. The intraoperative findings confirmed the conclusion of clinical and imaging studies performed preoperatively and radical excisions were performed. Histopathological examination (spindle cell neoplasm) and immunohistochemistry (CD117) confirmed EGIST. Both patients underwent Imatinib therapy following surgery with no evidence of disease recurrence or metastasis upon follow up. Although sharing histologic features with GIST, EGIST frequently demonstrates distinct characteristics that facilitate the proper diagnosis and management of EGIST. Since it is a rare and aggressive disease with a poor outcome, early detection and curative surgical resection remains the mainstay of treatment.

19.
Immune Netw ; 21(2): e13, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33996169

RESUMEN

Macrophages are important for the first line of defense against microbial pathogens. Integrin CD11b, which is encoded by Itgam, is expressed on the surface of macrophages and has been implicated in adhesion, migration, and cell-mediated cytotoxicity. However, the functional impact of CD11b on the inflammatory responses of macrophages upon microbial infection remains unclear. Here, we show that CD11b deficiency resulted in increased susceptibility to sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection by enhancing the pro-inflammatory activities of macrophages. Upon infection with MRSA, the mortality of Itgam knockout mice was significantly higher than that of control mice, which is associated with increased production of TNF-α and IL-6. In response to MRSA, both bone marrow-derived macrophages and peritoneal macrophages lacking CD11b produced elevated amounts of pro-inflammatory cytokines and nitric oxide. Moreover, CD11b deficiency upregulated IL-4-induced expression of anti-inflammatory mediators such as IL-10 and arginase-1, and an immunomodulatory function of macrophages to restrain T cell activation. Biochemical and confocal microscopy data revealed that CD11b deficiency augmented the activation of NF-κB signaling and phosphorylation of Akt, which promotes the functional activation of macrophages with pro-inflammatory and immunoregulatory phenotypes, respectively. Overall, our experimental evidence suggests that CD11b is a critical modulator of macrophages in response to microbial infection.

20.
BJUI Compass ; 2(4): 292-299, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35475302

RESUMEN

Objective: To describe a decade of our experience with a neo-urethral modification of ileal orthotopic neobladder (pitcher pot ONB). Multiple investigators have reported similar modifications. However, long-term longitudinal functional and quality of life (QOL) outcomes are lacking. Methods: Prospectively maintained hospital registry for 238 ONB patients comprising a mix of open and robotic surgery cohorts from 2007 to 2017, and minimum of 2 years of follow-up was retrospectively queried. QOL was evaluated using Bladder Cancer Index (BCI). Longitudinal trends of QOL domain parameters were analysed. List of perioperative variables that have a biologically plausible association with continence, potency, and post-operative BCI QOL sexual, urinary, and bowel domain scores was drawn. Variables included surgery type, Body Mass Index (BMI), T and N stage, neurovascular bundle (NVB) sparing, age, and related pre-operative BCI QOL domain score. Prognostic associations were analysed using multivariable Cox proportional hazard models and multilevel mixed-effects modeling. Results: The study comprised 80 and 158 patients who underwent open and robotic sandwich technique cohorts, respectively. Open surgery was associated with significantly higher "any" complication (40% vs 27%, P-value .050) and "major" complication rate (15% vs 11%, P-value .048). All patients developed a bladder capacity >400 cc with negligible post-void residual urine, and all but one patient achieved spontaneous voiding by the end of study period (<1% clean intermittent self-catheterization [CISC] rate). By 15 months, QOL for all three domains had recovered to reach a plateau. About 45% of patients achieved potency, and the median time to achieve day and night time continence was 9 and 12 months respectively. Lower age and NVBs spared during surgery were found to be significantly associated with the earlier achievement of potency, day and night time continence, as well as better urinary and sexual summary QOL scores. Conclusions: Pitcher pot neobladder achieves satisfactory long-term functional and QOL outcomes with negligible CISC rate. Results were superior with incremental nerves spared during surgery.

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