Clinical characteristics and outcomes of COVID-19 in patients with autoimmune hepatitis: A population-based matched cohort study

BACKGROUND Patients with autoimmune hepatitis(AIH) require life-long immunosuppressive agents that may increase the risk of poor corona virus disease 2019(COVID-19)outcomes.There is a paucity of large data at the population level to assess whether patients with AIH have an increased risk of severe diseases.AIM To evaluate the impact of pre-existing AIH on the clinical outcomes of patients with COVID-19.METHODS We conducted a population-based,multicenter,propensity score-matched cohort study with...     

骨质疏松性椎体骨折模型的建立

目的:建立大鼠的骨质疏松性椎体骨折模型,探讨骨折愈合程度与X射线、骨结构和力学性能的相互关系,以期能为临床治疗提供科学的指导和理论依据。方法:实验于2005-07/2006-07在解放军兰州军区总医院骨研所完成。实验动物:选择雌性SPF级8个月龄SD大鼠54只。实验分组:采用随机数字法将大鼠分为2组:骨质疏松组和对照组,每组27只。实验干预:骨质疏松组经双背侧手术切除卵巢,对照组行伪手术。术后3个月,所有动物麻醉下,采用L5椎体手术开窗刮除术区内松质骨方法建立人工椎体骨折模型。实验评估:于术后1,2,4,6,8,12周观察两组大鼠腰椎影像学、骨组织切片组织学与受累椎体力学性能。结果:54只SD大鼠全部进入结果分析。①影像学观察:术后两组X射线片示L5椎体有一骨折缺损透光区。对照组在术后6周时原透光区与周围骨质无明显差别,而骨质疏松组原透光区仍清晰可见,于8周时无明显差别。②组织学观察:两组软骨细胞在骨愈合1周时出现,形成软骨岛,但骨质疏松组软骨细胞每高倍视野数量明显少于对照组,另外,软骨细胞改建成成熟骨细胞,骨小梁形成数量,胶原纤维排列与对照组比较有显著性差异。③力学性能:在骨质愈合6～12周,L5椎体的最大载荷、弹性模量、最大应力明显低于同期对照组,差异有显著性意义(P<0.05)。结论:骨质疏松性椎体骨折SD大鼠模型,符合动物模型标准,可用于研究新骨形成与正常骨质结构关系,观察骨质疏松性椎体骨折愈合机制,并证明骨质疏松性松质骨骨折修复过程中,骨折愈合质量降低。     

Expression of pertussis toxin adenosine diphosphate-ribosyltransferase in a T-cell hybridoma reduces metastatic capacity

T-cell hybridomas are highly metastatic, and their in vitro invasiveness correlates with metastatic capacity. Invasion is blocked by pertussis toxin (PT), which adenosine diphosphate (ADP)-ribosylates G1-proteins, and we have provided evidence that the PT-sensitive signal stimulates leukocyte function-associated antigen-1 (LFA-1)-mediated adhesion required for invasion. PT pretreatment of TAM2D2 T-cell hybridoma cells reduced metastasis, but only to a limited extent. In the present study, we have transfected the cDNA of the PT ADP- ribosyltransferase S1 subunit into TAM2D2 cells to abrogate G1-protein function permanently. We report here a substantial reduction in the metastatic capacity of two transfectants, S05 and S09, in which 88% and 95% of the G1-proteins was ADP-ribosylated. Two-thirds of the mice injected with S09 cells were tumor-free. Metastasis to the liver was almost completely prevented and less metastases were formed in the spleen and kidneys. Metastasis formation by S05 cells in liver and spleen was much reduced, but in lymph nodes and peritoneal tissues, metastases occurred with a frequency similar to that of controls. We conclude that G1-proteins play an important role in T-cell hybridoma metastasis. We propose that the reduction in metastasis is due to diminished entry of tumor cells from the blood into tissues.     

Dental caries and erosion status of 12-year-old Hong Kong children

Background

We examined the association of alcohol use disorders (AUD) with adherence to and health-related quality of life (HRQOL) outcomes of antiretroviral treatment (ART) for HIV/AIDS patients.

Methods

A cross-sectional multi-site survey was conducted in 468 drug users and 648 non-drug users (age: 35.4 ± 7.0 years; 63.8% male) in 3 epicentres of Vietnam. AUD, ART adherence, and HRQOL were measured using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C), the self-reported Visual Analogue Scale (VAS), and the World Health Organization Quality of Life instrument (WHOQOL-HIV BREF).

Results

35.0% of drug users were hazardous drinkers, compared to 25.9% of non-drug users. 22.3% of drug users engaged in binge drinking, and 25.9% reported suboptimal ART adherence. Adjusting for propensity scores of AUD, patients who had either at-risk or binge drinking behaviour were about twice as likely to be treatment non-adherent as those who did not have AUD. Hazardous drinkers reported small to medium decrements in the Performance, Physical, Social, Spirituality, and Environment quality of life domains. Binge drinkers had a slightly higher score in Social dimension.

Conclusion

AUD is prevalent and negatively affecting adherence to and HRQOL outcomes of ART services in injection-driven HIV epidemics. Screening and intervention are recommended for AUD, especially during the stable periods of ART. Other social and psychological interventions might also enhance patients’ responses to and outcomes of ART in Vietnam.     

Giving a voice to patient experiences through the insights of pragmatism

As a philosophical position, pragmatism can be critiqued to distinguish truth only with methods that bring about desired results, predominantly with scientific enquiry. The article hopes to dismiss this oversimplification and propose that within mental health nursing, enquiry enlightened by pragmatism can be anchored to methods helping to tackle genuine human problems. Whilst pragmatists suggest one reality exists, fluctuating experiences and shifting beliefs about the world can inhabit within; hence, pragmatists propose reality has the potential to change. Moreover, pragmatism includes being cognisant of what works to whom reality concerns, making reality context-driven, with a view to understand how actions shape experiences so what is generated has usefulness. Hence, it somewhat follows pragmatism can inform mental health nursing, after all, nursing is a discipline of action, and awareness is needed in how actions produce experiences that patients find helpful. Given the principles of recovery are preferably adopted in mental health care, the paper will explore how pragmatism can help nurses move towards that goal; specifically, with patients voicing their experiences. This is because like pragmatism, recovery subscribes to hope that reality can progress, and through meaningful experiences and beliefs, patients have expertise about personal difficulties alongside how life may flourish, despite mental illness.     

Therapeutic plasma exchange in patients with life-threatening COVID-19: a randomised controlled clinical trial

Assessment of efficacy of therapeutic plasma exchange (TPE) following life-threatening COVID-19. This was an open-label, randomised clinical trial of ICU patients with life-threatening COVID-19 (positive RT-qPCR plus ARDS, sepsis, organ failure, hyperinflammation). Study was terminated after 87/120 patients enrolled. Standard treatment plus TPE (n = 43) versus standard treatment (n = 44), and stratified by PaO₂/FiO₂ ratio (>150 vs. ≤150), were compared. Primary outcomes were 35-day mortality and TPE safety. Secondary outcomes were association between TPE and mortality, improvement in SOFA score, change in inflammatory biomarkers, days on mechanical ventilation (MV), and ICU length of stay (LOS). Eighty-seven patients [median age 49 (IQR 34–63) years; 82.8% male] were randomised (44 standard care; 43 standard care plus TPE). Days on MV (P = 0.007) and ICU LOS (P = 0.02) were lower in the TPE group. 35-Day mortality was non-significantly lower in the TPE group (20.9% vs. 34.1%; Kaplan-Meier, P = 0.582). TPE was associated with increased lymphocytes and ADAMTS-13 activity and decreased serum lactate, lactate dehydrogenase, ferritin, d-dimers and interleukin-6. Multivariable regression analysis provided several predictors of 35-day mortality: PaO₂/FiO₂ ratio (HR, 0.98, 95% CI 0.96–1.00; P = 0.02]; ADAMTS-13 activity (HR, 0.89, 95% CI 0.82–0.98; P = 0.01); pulmonary embolism (HR, 3.57, 95% CI 1.43–8.92; P = 0.007). Post-hoc analysis revealed a significant reduction in SOFA score for TPE patients (P < 0.05). In critically-ill COVID-19 patients, addition of TPE to standard ICU therapy was associated with faster clinical recovery and no increased 35-day mortality.     

Improved delivery of miR-1296 loaded cationic nanoliposomes for effective suppression of triple negative breast cancer

Nowadays, microRNA is considered an attractive strategy for the effective treatment of cancer. A significant delivery of microRNA for cancer therapy remains a significant obstacle to target cancer cells. The restoring microRNA-1296 (miR-1296) has immense therapeutic efficacy in triple-negative breast cancer (TNBC). TNBC is an aggressive subtype of breast tumors with the progression of malignant transformation. This study aimed to develop a cationic nanoliposome that can serve as a miR-1296 carrier and studied its efficiency in TNBC. The efficacy of miR-1296 liposomes was evaluated on its apoptotic effect, cellular uptake, and potential chemotherapy sensitization in the TNBC cell line (MDA-MB-231). For in vitro viability study, the apoptotic effect was performed to validate protein expression using Alamar blue kit and western blot. The transfection of miR-1296 into TNBC cells was also investigated using cisplatin as a TNBC resistance drug. The fluorescent miR-1296-cy3 liposome was used for cellular uptake study. The miR-liposome was successfully prepared with a particle size of 123.6 ± 1.3 nm and encapsulation efficiency of 94.33%. A dose of 0.5 uM has significantly reduced the viability of MDA-MB-231 to be 33.45%±5.29 (P < 0.001). This result was validated by down-expression of CCND1, and PARP1, the miR-1296 receptor, and apoptosis marker. The image of the miR-1296-cy3 liposome showed cytoplasmic intracellular localization. It was found high sensitization of TNBC cell line for miR-1296 liposome compared to cisplatin (P < 0.001). Future in vivo research may answer questions concerning safety and stability. This study demonstrates that miR-191 liposomes may have promising clinical applications for TNBC therapy.     

Fluconazole nanoparticles prepared by antisolvent precipitation technique: Physicochemical,in vitro,ex vivo and in vivo ocular evaluation

The goal of this research was to prepare and characterize nanonized particles of the antifungal drug, fluconazole (FLZ) using antisolvent precipitation nanonization technique to improve its ocular permeation. The impact of various concentrations of different stabilizers, namely Pluronic F-127 (PL F 127), Kollicoat IR (KL), hydroxypropyl methylcellulose E3 (HPMC), xanthan gum (XG), polyvinyl pyrrolidone K30 (PVP), and sodium lauryl sulfate (SLS) upon the resulting nanoparticles was investigated. Additionally, the ex vivo release of the FLZ nanonized particles from ophthalmic gel bases was studied by using goat cornea, and the ocular pharmacokinetics of appropriate ophthalmic gel base containing optimized drug nanoparticle formula compared to the untreated drug were studied in rabbits. FLZ nanoparticles were successfully prepared with different concentrations of stabilizers. However, the effects of these stabilizers on nanoparticle size and zeta potential values varied according to the concentration and type of stabilizer used. Based on differential scanning calorimetry, the drug was in its amorphous state in the tested nanoparticle formulations. The results of ex vivo ocular diffusion of the FLZ nanoparticle gel formulations revealed an improvement compared to that with the FLZ untreated gel. Nanoparticle formula (F3) prepared by using 5% PL F127 showed small particle size (352 ± 6.1 nm) with zeta potential value of −18.3 mV with highest ex vivo release rate from goat cornea (100% after 6 h). Moreover, the AUC_0-8h from ocular application of FLZ from sodium alginate gel containing nanoparticle formula F3 was 1.4-fold higher than that after its administration in the untreated formula. Based on our findings, the ophthalmic gel formulations containing FLZ nanoparticles enhanced drug corneal permeation and improved the ocular pharmacokinetic parameters.     

Preparation,characterization, and antibacterial activity of diclofenac-loaded chitosan nanoparticles

Emerging antibiotic resistance necessitates the development of new therapeutic approaches. Many studies have reported the antimicrobial activity of diclofenac sodium (DIC) and chitosan nanoparticles (CNPs). Hence, this study aimed to prepare non-antibiotic DIC-loaded CNPs (DIC.CNPs) and characterize their in vitro antibacterial activity. DIC.CNPs were prepared from low and high molecular weight (LMW and HMW, respectively) chitosan using an ionic gelation method. Prepared NPs were characterized, and their antibacterial activity against gram-positive Staphylococcus aureus and Bacillus subtilis was evaluated using the agar diffusion and broth dilution methods. The particle size, polydispersity index (PDI), and encapsulation efficiency of the formulated DIC.CNPs increased with increasing MW of chitosan. The prepared NPs showed a narrow size distribution with low PDI values (0.18 and 0.24) and encapsulation efficiency (29.3% and 31.1%) for LMW.DIC.CNPs and HMW.DIC.CNPs, respectively. The in vitro release profile of DIC from the DIC.CNPs was biphasic with a burst release followed by slow release and was influenced by the MW of chitosan. DIC.CNPs exhibited significantly higher antibacterial activity against S. aureus (minimum inhibitory concentration [MIC₉₀] _LMW.DIC.CNPs?=?35?µg/mL and MIC_{90 HMW.DIC.CNPs}?=?18?µg/mL) and B. subtilis (MIC_{90 LMW.DIC.CNPs}?=?17.5?µg/mL and MIC_{90 HMW.DIC.CNPs}?=?9?µg/mL) than DIC alone did (MIC_{90 DIC}?=?250 and 50?µg/mL against S. aureus and B. subtilis, respectively). The antibacterial activity was influenced by pH and the MW of chitosan. Collectively, these results may suggest the potential usefulness of DIC.CNPs as non-antibiotic antibacterial agent necessitating further future studies to asses the stability of DIC.CNPs prepared.