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BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is usually a benign, yet underdiagnosed clinical condition associated with subacute to acute neurological manifestations primarily affecting white matter. PRES is reversible when recognized promptly and treated early by removal of the insulting factor; however, can lead to irreversible and life-threatening complications such as cerebral hemorrhage, cerebellar herniation, and refractory status epilepticus. METHODS: We utilized the National Inpatient Sample database provided by the Healthcare Cost and Utilization Project (HCUP-NIS) 2017 to investigate the demographic variables (age, sex, and race) for patients with PRES, concomitant comorbidities and conditions, inpatient complications, inpatient mortality, length of stay (LOS), and disposition. RESULTS: A total of 635 admissions for patients aged 18 years or older with PRES were identified. The mean age was 57.2 ± 0.6 years old with most encounters for female patients (71.7%, n = 455) and white as the most prevalent race. Half the patients in our study presented with seizures (50.1%, n = 318), sixty-three patients (9.9%) presented with vision loss, and sixty-four patients (10.1%) had speech difficulty. In addition, 45.5% of patients had hypertensive crisis (n = 289). 2.2% of hospitalizations had death as the outcome (n = 14). The mean LOS was 8.2 (±0.3) days, and the mean total charges were $92,503 (±$5758). Inpatient mortality differed between males and females (1.7% vs. 2.4%) and by race (3.6% in black vs. 1.8% in white) but was ultimately determined to be not statistically significant. Most patients who present with vision disturbance have a high risk of intracranial hemorrhage. Furthermore, end-stage renal disease, atrial fibrillation, and malignancy seemed to be linked with a very high risk of mortality. CONCLUSION: PRES, formerly known as reversible posterior leukoencephalopathy, is a neurological disorder with variable presenting symptoms. Although it is generally a reversible condition, some patients suffer significant morbidity and even mortality. To the best of our knowledge, this is the largest retrospective cohort of PRES admissions that raises clinician awareness of clinical characteristics and outcomes of this syndrome.
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Síndrome da Leucoencefalopatia Posterior , Hemorragia Cerebral , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Síndrome da Leucoencefalopatia Posterior/complicações , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome da Leucoencefalopatia Posterior/epidemiologia , Síndrome da Leucoencefalopatia Posterior/mortalidade , Estudos RetrospectivosRESUMO
Thrombotic microangiopathy (TMA) is characterized by systemic microvascular thrombosis, target organ injury, anemia and thrombocytopenia. Thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome and Shiga toxin E-coli-related hemolytic uremic syndrome are the three common forms of TMAs. Traditionally, TMA is encountered during pregnancy/postpartum period, malignant hypertension, systemic infections, malignancies, autoimmune disorders, etc. Recently, the patients presenting with trauma have been reported to suffer from TMA. TMA carries a high morbidity and mortality, and demands a prompt recognition and early intervention to limit the target organ injury. Because trauma surgeons are the first line of defense for patients presenting with trauma, the prompt recognition of TMA for these experts is critically important. Early treatment of post-traumatic TMA can help improve the patient outcomes, if the diagnosis is made early. The treatment of TMA is also different from acute blood loss anemia namely in that plasmapheresis is recommended rather than platelet transfusion. This article familiarizes trauma surgeons with TMA encountered in the context of trauma. Besides, it provides a simplified approach to establishing the diagnosis of TMA. Because trauma patients can require multiple transfusions, the development of disseminated intravascular coagulation must be considered. Therefore, the article also provides different features of disseminated intravascular coagulation and TMA. Finally, the article suggests practical points that can be readily applied to the management of these patients.
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Cirurgiões , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Ferimentos e Lesões/complicações , Ferimentos e Lesões/cirurgia , Proteína ADAMTS13/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/prevenção & controle , Feminino , Humanos , Masculino , Gravidez , Microangiopatias Trombóticas/mortalidade , Microangiopatias Trombóticas/terapia , Ferimentos e Lesões/terapiaRESUMO
Co-drug, or mutual-prodrug, is a drug design approach consisting of covalently linking two active drugs so as to improve the pharmacokinetics and/or pharmacodynamics properties of one or both drugs. Co-drug strategy has proven good success in overcoming undesirable properties such as absorption, poor bioavailability, nonspecificity, and gastrointestine tract (GIT) side effects. In this work, we successfully developed a co-drug of 14-hydroxytylophorine, a phenanthroindolizidine derivative with remarkable antiproliferative activity, and dichloroacetate, a known inhibitor of pyruvate dehydrogenase kinase. Dichloroacetate steers tumour cell metabolism from glycolysis back to glucose oxidation, which in turn reverses the Warburg effect and renders tumour cells with a proliferative disadvantage. The obtained co-drugs retained the cytotoxicity of 14-hydroxytylophorine. However, they showed similar unselectivity towards normal cells.
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Antineoplásicos/farmacologia , Desenho de Fármacos , Indóis/farmacologia , Fenantrenos/farmacologia , Pró-Fármacos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Células CHO , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cricetulus , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/síntese química , Indóis/química , Estrutura Molecular , Fenantrenos/síntese química , Fenantrenos/química , Pró-Fármacos/síntese química , Pró-Fármacos/química , Solubilidade , Relação Estrutura-AtividadeRESUMO
Phenanthroindolizidines are naturally occurring alkaloids mainly isolated from different species of Asclepiadaceae. These alkaloids are characterized by an excellent anticancer activity against a very wide range of cancerous cell lines including those who are multi drug resistant. Nevertheless, phenanthroindolizidines are associated with sever neurotoxicity that prevented any candidate from this family to pass the clinical trials. A number of boron-based analogues of (R)-6-O-desmethylantofine have been synthesised. Their physochemical properties were evaluated, same as their in-vitro antiproliferative activity. The pinacol boronate ester derivative (3) showed interesting cytotoxicity against a panel of cancerous cell lines attested by a cancer cell growth-inhibitory potency (GI50) as low as 30 nM.
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Antineoplásicos/farmacologia , Ácidos Borônicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Ácidos Borônicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Autoimmune diseases can result in additional symptoms and complications impacting various organ systems beyond the joints. These can affect the eyes, skin, respiratory, cardiac, and renal systems. Recognizing and understanding these diverse manifestations, such as the severe eye issues seen in rheumatoid arthritis (RA) and the potentially life-threatening Felty syndrome, is crucial for clinicians to promptly identify and treat these conditions effectively. In this case presentation, we report on a patient admitted for bilateral scleritis, which was found to be secondary to multiple autoimmune syndrome type 3. During the patient's hospital stay, Felty syndrome was incidentally diagnosed due to the observed combination of RA, splenomegaly, and absolute neutropenia. Prompt recognition of this condition allowed the patient to receive appropriate care, including oral steroids, hydroxychloroquine, and methotrexate, decreasing the risk of severe complications.
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Renal cell carcinoma (RCC) is notorious for spreading to various organs, however, its occurrence in the gastrointestinal (GI) tract is uncommon and poses diagnostic challenges due to vague symptoms. Here, we present the case of a 64-year-old man experiencing recurrent RCC metastasis in the GI tract. He presented with multiple episodes of hematochezia and was found to have masses in the colon, liver, and peritoneum, with histopathology confirming RCC. The patient underwent systemic chemotherapy and palliative radiation therapy, leading to symptom relief. This case emphasizes the rarity of RCC metastasizing to the GI tract and the importance of timely recognition and frequent surveillance during the remission phase to detect recurrence.
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BACKGROUND: Pylephlebitis is an extremely rare form of septic thrombophlebitis involving the portal vein, carrying high rates of morbidity and mortality. CASE SUMMARY: We present a case of a 42-year-old male with no past medical history who presented with acute onset of abdominal pain and altered mental status with laboratory tests demonstrating new-onset acute liver failure. Pylephlebitis was determined to be the underlying etiology due to subsequent workup revealing polymicrobial gram-negative anaerobic bacteremia and complete thrombosis of the main and left portal veins. To our knowledge, this is the first documented case of acute liver failure as a potential life-threatening complication of pylephlebitis. CONCLUSION: Our case highlights the importance of considering pylephlebitis in the broad differential for abdominal pain, especially if there are co-existing risk factors for hypercoagulability. We also demonstrate that fulminant hepatic failure in these patients can potentially be reversible with the immediate initiation of antibiotics and anticoagulation.
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Helicases have emerged as promising targets for the development of antiviral drugs; however, the family remains largely undrugged. To support the focused development of viral helicase inhibitors we identified, collected, and integrated all chemogenomics data for all available helicases from the ChEMBL database. After thoroughly curating and enriching the data with relevant annotations we have created a derivative database of helicase inhibitors which we dubbed Heli-SMACC (Helicase-targeting SMAll Molecule Compound Collection). The current version of Heli-SMACC contains 20,432 bioactivity entries for viral, human, and bacterial helicases. We have selected 30 compounds with promising viral helicase activity and tested them in a SARS-CoV-2 NSP13 ATPase assay. Twelve compounds demonstrated ATPase inhibition and a consistent dose-response curve. The Heli-SMACC database may serve as a reference for virologists and medicinal chemists working on the development of novel helicase inhibitors. Heli-SMACC is publicly available at https://smacc.mml.unc.edu.
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Background Post-acute care (PAC) centers are facilities used for recuperation, rehabilitation, and symptom management in an effort to improve the long-term outcomes of patients. PAC centers include skilled nursing facilities, inpatient rehabilitation facilities, and long-term care hospitals. In the 1990s, Medicare payment reforms significantly increased the discharge rates to PAC centers and subsequently increased the length of stay (LOS) among these patient populations. Over the last several years, there have been national initiatives and multidisciplinary approaches to improve safe discharge rates to home. Multiple studies have shown that patients who are discharged to home have decreased rates of 30-day readmissions, reduced short-term mortality, and an improvement in their activities of daily living. Objectives This study aimed to investigate how multidisciplinary approaches could improve a single institution's discharge rates to home. In doing so, we aim to lower hospital readmission rates, hospital length of stay, morbidity and mortality rates, and healthcare-associated costs. Methods A retrospective single-institution cohort study was implemented at Jersey Shore University Medical Center (JSUMC). Data from January 2015 to December 2019 served as the control period, compared to the intervention period from January 2020 to January 2024. Patients were either admitted to JSUMC teaching faculty, hospitalists, or "others," which is composed of various medical and surgical subspecialists. Interventions performed to improve home discharge rates can be categorized into the following: physician education, patient education, electronic medical record (EMR) initiatives, accountability, and daily mobility initiatives. All interventions were performed equally across the three patient populations. The primary endpoint was the proportion of patients discharged to home. Results There were 190,699 patients, divided into a pre-intervention group comprising 98,885 individuals and a post-intervention group comprising 91,814 patients. Within the pre-intervention group, the faculty attended to 8,495 patients, hospitalists cared for 39,145 patients, and others managed 51,245 patients. In the post-intervention period, the faculty oversaw 8,014 patients, hospitalists attended to 35,094 patients, and others were responsible for 48,706 patients. After implementing a series of multidisciplinary interventions, there was a significant increase in the proportion of patients discharged home, rising from 74.9% to 80.2% across the entire patient population. Specifically, patients under the care of the faculty experienced a more substantial improvement, with a discharge rate increasing from 73.6% to 84.4%. Similarly, the hospitalists exhibited a rise from 69.4% to 74.3%, and the others demonstrated an increase from 79.3% to 83.7%. All observed changes yielded a p-value < 0.001. Conclusions By deploying a multifaceted strategy that emphasized physician education, patient education, EMR initiatives, accountability measures, and daily mobility, there was a statistically significant increase in the rate of patient discharges to home. These initiatives proved to be cost-effective and led to a tangible reduction in healthcare-associated costs and patient length of stay. Further studies are required to look into the effect on hospital readmission rates and morbidity and mortality rates. The comprehensive approach showcased its potential to optimize patient outcomes.
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We recently reported that lecithin:cholesterol acyltransferase (LCAT) knock-out mice, particularly in the LDL receptor knock-out background, are hypersensitive to insulin and resistant to high fat diet-induced insulin resistance (IR) and obesity. We demonstrated that chow-fed Ldlr-/-xLcat+/+ mice have elevated hepatic endoplasmic reticulum (ER) stress, which promotes IR, compared with wild-type controls, and this effect is normalized in Ldlr-/-xLcat-/- mice. In the present study, we tested the hypothesis that hepatic ER cholesterol metabolism differentially regulates ER stress using these models. We observed that the Ldlr-/-xLcat+/+ mice accumulate excess hepatic total and ER cholesterol primarily attributed to increased reuptake of biliary cholesterol as we observed reduced biliary cholesterol in conjunction with decreased hepatic Abcg5/g8 mRNA, increased Npc1l1 mRNA, and decreased Hmgr mRNA and nuclear SREBP2 protein. Intestinal NPC1L1 protein was induced. Expression of these genes was reversed in the Ldlr-/-xLcat-/- mice, accounting for the normalization of total and ER cholesterol and ER stress. Upon feeding a 2% high cholesterol diet (HCD), Ldlr-/-xLcat-/- mice accumulated a similar amount of total hepatic cholesterol compared with the Ldlr-/-xLcat+/+ mice, but the hepatic ER cholesterol levels remained low in conjunction with being protected from HCD-induced ER stress and IR. Hepatic ER stress correlates strongly with hepatic ER free cholesterol but poorly with hepatic tissue free cholesterol. The unexpectedly low ER cholesterol seen in HCD-fed Ldlr-/-xLcat-/- mice was attributable to a coordinated marked up-regulation of ACAT2 and suppressed SREBP2 processing. Thus, factors influencing the accumulation of ER cholesterol may be important for the development of hepatic insulin resistance.
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Colesterol/metabolismo , Estresse do Retículo Endoplasmático , Deficiência da Lecitina Colesterol Aciltransferase/metabolismo , Fígado/metabolismo , Fosfatidilcolina-Esterol O-Aciltransferase , Receptores de LDL/metabolismo , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/biossíntese , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Colesterol/genética , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/fisiologia , Regulação da Expressão Gênica/genética , Resistência à Insulina/genética , Deficiência da Lecitina Colesterol Aciltransferase/genética , Deficiência da Lecitina Colesterol Aciltransferase/patologia , Lipoproteínas/biossíntese , Lipoproteínas/genética , Fígado/patologia , Proteínas de Membrana Transportadoras/biossíntese , Proteínas de Membrana Transportadoras/genética , Camundongos , Camundongos Knockout , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores de LDL/genética , Esterol O-Aciltransferase/genética , Esterol O-Aciltransferase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Esterol O-Aciltransferase 2RESUMO
BACKGROUND: Canine GM1 gangliosidosis is a fatal disease in the Shiba Inu breed, which is one of the most popular traditional breeds in Japan and is maintained as a standard breed in many countries. Therefore, it is important to control and reduce the prevalence of GM1 gangliosidosis for maintaining the quality of this breed and to ensure supply of healthy dogs to prospective breeders and owners. This molecular epidemiological survey was performed to formulate an effective strategy for the control and prevention of this disease. RESULTS: The survey was carried out among 590 clinically unaffected Shiba Inu dogs from the 8 districts of Japan, and a genotyping test was used to determine nation-wide and regional carrier frequencies. The number and native district of affected dogs identified in 16 years from 1997 to June 2013 were also surveyed retrospectively. Of the 590 dogs examined, 6 dogs (1.02%, 6/590) were carriers: 3 dogs (2.27%, 3/132) from the Kinki district and the other 3 dogs from the Hokkaido, Kanto, and Shikoku districts. The retrospective survey revealed 23 affected dogs, among which, 19 dogs (82.6%) were born within the last 7 years. Of the 23 affected dogs, 12 dogs (52.2%) were from the Kinki district. Pedigree analysis demonstrated that all the affected dogs and carriers with the pedigree information have a close blood relationship. CONCLUSIONS: Our results showed that the current carrier frequency for GM1 gangliosidosis is on the average 1.02% in Japan and rather high in the Kinki district, which may be related to the high prevalence observed over the past 16 years in this region. This observation suggests that carrier dogs are distributed all over Japan; however, kennels in the Kinki district may face an increased risk of GM1 gangliosidosis. Therefore, for effective control and prevention of this disease, it is necessary to examine as many breeding dogs as possible from all regions of Japan, especially from kennels located in areas with high prevalence and carrier frequency.
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Doenças do Cão/genética , Gangliosidose GM1/veterinária , Animais , Cruzamento , Doenças do Cão/epidemiologia , Cães/genética , Gangliosidose GM1/epidemiologia , Gangliosidose GM1/genética , Predisposição Genética para Doença/genética , Genótipo , Heterozigoto , Japão/epidemiologia , Epidemiologia Molecular , Linhagem , Prevalência , Estudos RetrospectivosRESUMO
This case report describes an unusual manifestation of hemophilia B, in the form of a lateral chest wall hematoma. A 27-year-old hemophiliac male was found to have a lateral chest wall hematoma after presenting with back pain associated with localized chest wall swelling. Even more unusual than the location of his hematoma was the absence of any preceding triggers such as a fall or trauma to the area. To our knowledge, this is the first reported case of its kind in a patient with inherited hemophilia B. We believe the reporting of such rare presentations increases awareness of these possibilities and thus aids in the prompt diagnosis and treatment of other similar cases when they are encountered.
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The presence of gas and free air in the extraluminal space of the intestines is known as pneumatosis intestinalis (PI). There are many different causes of this finding, including gastrointestinal, pulmonary, autoimmune, and many more. It is often difficult to differentiate the etiology and clinical importance of the radiographic evidence on pneumatosis intestinalis due to the unclear pathophysiology causing the disease. To complicate things further, the ominous sign of portal venous gas poses the question of whether surgical intervention is needed. We report two cases both with clinical and radiographic evidence of secondary pneumatosis intestinalis with an associated sinister finding of portal venous gas. The cases differ by urgent surgical intervention versus observation before surgery. In this case series, we emphasize the importance of recognizing the radiographic finding and stress the need for further research to standardize a plan of care, including indications for surgery. We encourage more cases like this to be reported to aid in diagnosing and treating this condition early on with the aim of improving the mortality associated with it.
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VEXAS (vacuoles, E1 enzyme, X-linked, auto-inflammatory, somatic) syndrome is a newly defined illness that bridges hematology, oncology, and rheumatology. Its pathophysiology originates in a mutation in the UBA1 gene that leads to a defect in ubiquitination resulting in a severe systemic inflammatory syndrome. It is associated with significant morbidity and mortality; however, data are scarce due to limited cases described in the literature. Here we describe a case of a male in his 60s who was referred to hematology-oncology due to progressive dyspnea, poor oral intake, and weight loss. He was diagnosed with relapsing polychondritis 2 years prior; however, his symptoms did not improve despite treatment. He was ultimately diagnosed with VEXAS syndrome with a mutation in UBA1 (ubiquitin-like modifier activating enzyme 1) and a concurrent SQSTM1 mutation. In addition, the coexistence of two mutations in the ubiquitination pathway in the same patient has not been reported to date. This patient and the treatment course were compared to pre-existing literature to increase awareness and improve the medical management of VEXAS syndrome.
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Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a rare abnormality comprising a series of symptoms that make up a syndrome. It usually happens during pregnancy or right after delivery. We describe a case of a 31-year-old female G4P2A2 (Gravida 4 Para 2 Abortions 2) who presented to the hospital for normal vaginal delivery but immediately postpartum developed HELLP syndrome. Acute fatty liver of pregnancy was a differential that the patient also met the criteria for. Her condition improved after starting her on plasmapheresis without considering hepatic transplantation. We emphasize distinguishing the overlap of symptoms between HELLP syndrome vs. acute fatty liver of pregnancy and the outcomes of plasmapheresis in managing HELLP syndrome without needing hepatic transplantation.
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Appendiceal mucocele is an extremely rare pathology accounting for 0.3-0.7% of all appendiceal pathology. It is characterized by appendiceal lumen dilatation by mucinous secretion collection. Though abdominal imaging and tissue Biopsy aids in diagnosis, suspicion should arise when a slight bulge or protrusion is seen on colonoscopy. We present a case of incidental appendiceal bulge found on a routine colonoscopy to evaluate abdominal pain that led to prompt diagnosis and management of appendiceal mucocele.
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The in vitro and in vivo efficacy of three biocontrol agents, Trichoderma viride, Pseudomonas fluorescence, and Bacillus subtilis, were tested against Rhizoctonia solani (AG-4) infection compared to two conventional fungicides (Rizolex-T 50%wettable powder and Amistar 25%). Antifungal enzyme activity was assayed in the culture filtrate of the biocontrol agents. The impact of the tested biocontrol agents on the induction of the coriander immune system was investigated against R. solani by assessing the resistance-related enzymes and compounds in biocontrol agent-treated plants compared with the control. The obtained results revealed that all tested biocontrol agents significantly reduced the linear growth of R. solani, and T. viride recorded the highest inhibition percentage. This could be linked to the ability of T. viride to produce higher activities of antimicrobial enzymes, i.e., cellulase, chitinase, and protease, compared to P. fluorescence and B. subtilis. Applying the tested biocontrol agents significantly alleviated pre- and post-emergence damping-off and root rot/wilt diseases of infected coriander compared with untreated plants. The tested biocontrol agents exhibited significantly higher germination percentage and vigor index of the coriander than the tested fungicides. The tested biocontrol agents significantly minimized the reduction of photosynthetic pigments induced by R. solani. In addition, the results showed a significant increase in enzymes/molecules (i.e., phenylalanine, catalase, peroxidase, catalase, superoxide dismutase, phenylalanine ammonia-lyase, phenolics, ascorbic acids, and salicylic acid) involved directly and indirectly in coriander resistance to R. solani. The principal component analysis of the recorded data recommended the role of the high accumulation of oxidative parameters (hydrogen peroxide and lipid peroxidation) and the inhibition of phenolic compounds in the downregulation of coriander resistance against R. solani. The heatmap analysis results revealed that biocontrol agents, especially Trichoderma, enhanced the resistance against R. solani via the stimulation of salicylic acid, phenolics, and antioxidant enzymes. Overall, the data recommended the efficacy of biocontrol agents, especially T. viride, against R. solani infecting coriander plants, which could be an efficient and a safer alternative to conventional fungicides.
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Background Early ambulation during acute hospitalization has been associated with improved clinical outcomes for patients. Despite the benefits of mobility in the hospital setting, physical therapists and nursing staff are often constrained by time. Mobility technicians (MTs) are individuals with specialized training who have emerged as a potential solution by providing safe ambulation for patients during their hospital stay. Objectives The purpose of this quality improvement project was to investigate the impact of MTs on clinical and financial outcomes for admitted patients at a high-volume tertiary institution. Methods A quality improvement project was implemented at Jersey Shore University Medical Center, Neptune City, from October 2022 to March 2023. The study was a prospective, single-institution cohort study and included patients admitted to two medical floors. Patients were divided into an experimental group that received services from MTs and a control group that did not receive this service but was eligible based on clinical status. The primary endpoint was the proportion of patients discharged to home. Secondary outcomes included the length of stay and financial impact. Results A total of 396 admitted patients were included, with 222 patients in the MT group and 174 in the non-MT group. Patients in the MT group were discharged home more frequently, at a rate of 79.7% compared to 66.1% for patients in the non-MT group (p = 0.002). MTs contributed to an average 2.4-day reduction in the length of hospital stay (7.8 days vs. 10.2 days, p = 0.007). The MT intervention led to an estimated net savings of $148,500 during the six-month study period. Additionally, 2.9 daily hospital beds were created. Conclusion Implementing an MT program significantly increased the discharge-to-home rates and decreased hospital length of stay. Preliminary analysis suggests that this intervention is cost-effective and can assist institutions in managing increased hospital capacity strain through the creation of additional hospital beds.
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The spread of multidrug-resistant tuberculosis (MDR-TB) is a growing problem in many countries worldwide. Resistance to one of the primary first-line drugs, rifampicin, is caused by mutations in the Mycobacterium tuberculosis rpoB gene. So-called borderline rpoB mutations confer low-level resistance, in contrast to more common rpoB mutations which confer high-level resistance. While some borderline mutations show lower fitness in vitro than common mutations, their in vivo fitness is currently unknown. We used a dataset of 394 whole genome sequenced MDR-TB isolates from Bangladesh, representing around 44â% of notified MDR-TB cases over 6 years, to look at differences in transmission clustering between isolates with borderline rpoB mutations and those with common rpoB mutations. We found a relatively low percentage of transmission clustering in the dataset (34.8â%) but no difference in clustering between different types of rpoB mutations. Compensatory mutations in rpoA, rpoB, and rpoC were associated with higher levels of transmission clustering as were lineages two, three, and four relative to lineage one. Young people as well as patients with high sputum smear positive TB were more likely to be in a transmission cluster. Our findings show that although borderline rpoB mutations have lower in vitro growth potential this does not translate into lower transmission potential or in vivo fitness. Proper detection of these mutations is crucial to ensure they do not go unnoticed and spread MDR-TB within communities.
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Proteínas de Bactérias , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Bangladesh/epidemiologia , Mutação , Rifampina/farmacologia , Mycobacterium tuberculosis/genética , Proteínas de Bactérias/genéticaRESUMO
Naphthyridine-based inhibitors were synthesized to yield a potent and cell-active inhibitor of casein kinase 2 (CK2). Compound 2 selectively inhibits CK2α and CK2α' when profiled broadly, thereby making it an exquisitely selective chemical probe for CK2. A negative control that is structurally related but lacks a key hinge-binding nitrogen (7) was designed on the basis of structural studies. Compound 7 does not bind CK2α or CK2α' in cells and demonstrates excellent kinome-wide selectivity. Differential anticancer activity was observed when compound 2 was profiled alongside a structurally distinct CK2 chemical probe: SGC-CK2-1. This naphthyridine-based chemical probe (2) represents one of the best available small molecule tools with which to interrogate biology mediated by CK2.