Nanomedicine for acute respiratory distress syndrome: The latest application,targeting strategy,and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air–blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.     

Anal incontinence in women with recurrent obstetric anal sphincter rupture: a case control study

Objectives: To determine the risk of recurrent anal sphincter rupture (ASR), and compare the risk of anal incontinence (AI) after recurrent ASR, with that seen in women with previous ASR who deliver by caesarean section or vaginally without sustaining a recurrent ASR.

Methods: Women with recurrent ASR between January 2000 and June 2011 were identified at two delivery wards in Copenhagen. The women answered a questionnaire with a validated scoring system for AI (St. Mark`s score), and the results were compared with those obtained in two control groups: women with subsequent uncomplicated vaginal delivery or caesarean section.

Results: There were 93?437 vaginal deliveries. ASR occurred in 5.5% (n?=?2851) of the nulliparous and 1.5% (n?=?608) of the multiparous women. Recurrent ASR occurred in 8% (n?=?49) of whom 50% reported symptoms of AI. We found no difference in the occurrence of AI between women with recurrent ASR, and those who delivered vaginally without repeat ASR (p?=?0.37; OR?=?2.0) or by caesarean section (p?=?0.77; OR?=?1.3).

Conclusion: Women with a past history of ASR have an 8% risk of recurrence. AI affects half of the women with recurrent ASR. Larger studies are required to confirm our findings.     

Does dystocia during labor pose a risk factor for another non-progressive labor during the subsequent delivery?

Objective: To establish whether failure to progress during labor poses a risk factor for another non-progressive labor (NPL) during the subsequent delivery.

Methods: A retrospective cohort study including singleton pregnancies that failed to progress during the previous labor and resulted in a cesarean section (CS) was conducted. Parturients were classified into three groups for both previous and subsequent labors: CS due to NPL stage I, stage II and an elective CS as a comparison group.

Results: Of 202?462 deliveries, 10?654 women met the inclusion criteria: 3068 women were operated due to NPL stage I and 1218 due to NPL stage II. The comparison group included 6368 women. Using a multivariable logistic regression models, NPL stage I during the previous delivery was found as an independent risk factor for another NPL stage I in the subsequent labor (adjusted odds ratio [OR]?=?2.9; 95% confidence interval [CI]?=?2.4–3.7; p?subsequent labor (adjusted OR?=?1.4; 95% CI?=?1.1–2.1; p?=?0.033; adjusted OR?=?5.3; 95% CI?=?3.7–7.5; p?Conclusion: A previous CS due to a NPL is an independent risk factor for another NPL in the subsequent pregnancy and for recurrent cesarean delivery.     

Subsequent Malignant Neoplasm of Bone in Children and Adolescent—Possibility of Multimodal Treatment

Background: In recent years, modifications of treatment protocols introduced in pediatric oncology have resulted in a significant improvement in treatment outcomes. Unfortunately, the probability of subsequent malignant neoplasm (SMN) in this group of patients is 3 to 6 times higher than the general age-matched population. In this study, we sought to evaluate the treatment options for patients with secondary bone tumors after prior anti-cancer therapy. Materials and Methods: Twenty-four patients (median age 12.9 years) with subsequent malignant bone tumors were treated according to oncological guidelines for bone sarcoma during the period 1991–2020. All patients had a standard tumor imaging and laboratory evaluation. All toxicities were documented. Results: The median time from the first neoplasm to SMN was 7.6 years (range 2.4 to 16.3 years). All patients received chemotherapy and underwent surgery as a local control procedure. Two patients with Ewing sarcoma had additional radiation on the tumor bed. A complete response was achieved in 20 patients. With a median follow-up of 18.3 years (range 5.7 to 40.3 years), 18 patients (75%) are alive. The estimated 5-year post-subsequent bone malignant neoplasm survival was 74.5% (95% CI 55–95%). Fourteen patients required chemotherapy dose modification, and doxorubicin was discontinued in seven patients. One patient required a renal transplant two years after treatment. There were no other significant toxicities. Conclusions: The treatment of bone SMNs can be effective, although in many patients it is necessary to reduce the doses of drugs. Early detection and aggressive treatment can improve the outcome.     

Practical model description of peripheral neural excitation in cochlear implant recipients: 3. ECAP during bursts and loudness as function of burst duration

In this, the third paper of the series, the loudness of low-rate bursts of electrical pulses was measured as a function of the burst duration, in subjects implanted with the Nucleus^® 24 cochlear implant system (three with straight and two with Contour™ electrode arrays). In order to help distinguish between the contributions of peripheral and more central effects, the ECAP was recorded to the individual pulses comprising the bursts, using the Neural Response Telemetry™ (NRT™) system. At a pulse rate of 250 pulses/s, the ECAP amplitude did not decrease greatly during the bursts: the mean reduction factor was 0.89. The time-constant for summation of the loudness contributions from the pulses comprising a burst was found to be larger than that associated with normal hearing. In addition, the first pulse of a pulse train was found to contribute much more to the overall loudness than did the subsequent pulses, although a corresponding difference was not observed in the ECAP recordings. These results establish a necessary connection between the essentially single-pulse model, developed in the fourth and fifth papers of the series, and the psychophysical data for pulse bursts, but they also have broader implications.     

Differential effects of semantic processing on memory encoding

Deeper semantic processing of words leads to enhanced memory encoding (depth of processing effect). The left inferior prefrontal cortex (LIPC) and the left hippocampus are known to be involved in this effect. We tested the hypothesis that different semantic encoding processes contribute qualitatively differently to memory encoding. In a memory experiment using functional magnetic resonance imaging, we compared three different encoding tasks: a nonsemantic alphabetical, an animacy decision, and a size comparison tasks. Recognition memory was tested subsequently. We hypothesized that the size comparison task would activate brain areas involved in the processing of object features and that this would be associated with successful memory encoding. Results showed that the size comparison task led to significantly better memory encoding than the two other tasks. As with the animacy decision task, it led to stronger activation of the LIPC and left hippocampus than the nonsemantic task. Both regions also had stronger activations for later remembered than for nonremembered words. The size comparison task additionally led to stronger activation in the left anterior fusiform gyrus, which was also associated with successful memory encoding. We conclude that different types of semantic processing affect memory encoding based on distinguishable brain processes. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Risk factors for poor outcome of untreated arteriovenous malformation

This study was conducted to determine risk factors for poor outcome in the natural history of arteriovenous malformation (AVM). We statistically analysed the correlation between clinical or angiographical findings and clinical outcomes for 55 cases of untreated AVM. Subsequent haemorrhage from AVMs was the only significant risk factor for poor outcome (P< 0.0001). The odds ratio was 44.56 with a 95% confidence interval (CI) from 4.80 to 413.90. Risk factors for subsequent haemorrhage from AVMs were also determined. The size (P = 0.0483) and location (P = 0.0147) of an AVM were significant risk factors for subsequent haemorrhage. The odds ratios were 3.97 with a 95% CI from 1.18 to 13.33 and 3.89 with a 95% CI from 1.10 to 13.72, respectively. AVMs of more than 60 mm, and deep or infratentorial AVMs had more chance of subsequent haemorrhage, and hence of a poor outcome. We propose using an aggressive multidisciplinary approach to treating these AVMs.