Forward and Reverse Middle Ear Transmission in Gerbil with a Normal or Spontaneously Healed Tympanic Membrane

Tympanic membranes (TM) that have healed spontaneously after perforation present abnormalities in their structural and mechanical properties; i.e., they are thickened and abnormally dense. These changes result in a deterioration of middle ear (ME) sound transmission, which is clinically presented as a conductive hearing loss (CHL). To fully understand the ME sound transmission under TM pathological conditions, we created a gerbil model with a controlled 50% pars tensa perforation, which was left to heal spontaneously for up to 4 weeks (TM perforations had fully sealed after 2 weeks). After the recovery period, the ME sound transmission, both in the forward and reverse directions, was directly measured with two-tone stimulation. Measurements were performed at the input, the ossicular chain, and output of the ME system, i.e., at the TM, umbo, and scala vestibuli (SV) next to the stapes. We found that variations in ME transmission in forward and reverse directions were not symmetric. In the forward direction, the ME pressure gain decreased in a frequency-dependent manner, with smaller loss (within 10 dB) at low frequencies and more dramatic loss at high frequency regions. The loss pattern was mainly from the less efficient acoustical to mechanical coupling between the TM and umbo, with little changes along the ossicular chain. In the reverse direction, the variations in these ears are relatively smaller. Our results provide detailed functional observations that explain CHL seen in clinical patients with abnormal TM, e.g., caused by otitis media, that have healed spontaneously after perforation or post-tympanoplasty, especially at high frequencies. In addition, our data demonstrate that changes in distortion product otoacoustic emissions (DPOAEs) result from altered ME transmission in both the forward and reverse direction by a reduction of the effective stimulus levels and less efficient transfer of DPs from the ME into the ear canal. This confirms that DPOAEs can be used to assess both the health of the cochlea and the middle ear.     

Impact of modified-release opioid use on clinical outcomes following total hip and knee arthroplasty: a propensity score-matched cohort study

Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3–13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.     

Nanotechnology for colorectal cancer detection and treatment

Colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related mortality in the United States. Across the globe, people in the age group older than 50 are at a higher risk of CRC. Genetic and environmental risk factors play a significant role in the development of CRC. If detected early, CRC is preventable and treatable. Currently, available screening methods and therapies for CRC treatment reduce the incidence rate among the population, but the micrometastasis of cancer may lead to recurrence. Therefore, the challenge is to develop an alternative therapy to overcome this complication. Nanotechnology plays a vital role in cancer treatment and offers targeted chemotherapies directly and selectively to cancer cells, with enhanced therapeutic efficacy. Additionally, nanotechnology elevates the chances of patient survival in comparison to traditional chemotherapies. The potential of nanoparticles includes that they may be used simultaneously for diagnosis and treatment. These exciting properties of nanoparticles have enticed researchers worldwide to unveil their use in early CRC detection and as effective treatment. This review discusses contemporary methods of CRC screening and therapies for CRC treatment, while the primary focus is on the theranostic approach of nanotechnology in CRC treatment and its prospects. In addition, this review aims to provide knowledge on the advancement of nanotechnology in CRC and as a starting point for researchers to think about new therapeutic approaches using nanotechnology.     

腹腔镜与开腹手术治疗长径5~10 cm中危原发性胃间质瘤的安全性和有效性比较

目的　比较腹腔镜和开腹手术治疗长径5~10 cm的中危胃间质瘤的安全性和有效性，并评估患者术后使用伊马替尼辅助治疗是否有明显益处。方法　回顾性分析2010年1月—2020年7月在南京大学医学院附属鼓楼医院接受手术治疗的72例长径在5~10 cm的中危胃间质瘤患者资料。其中腹腔镜手术组28例，开腹手术组44例。比较两组患者基本资料、病理特征、围手术期结果、住院总费用。对比术后使用和不使用伊马替尼辅助治疗的生存率。结果　开腹组和腹腔镜组临床病理特征差异无统计学意义（P>0.05）。腹腔镜组术后并发症发生率为32.1%（9/28），开腹组为52.3%（23/44），两组比较差异无统计学意义（P=0.094）。与开腹组相比，腹腔镜组总住院时间明显缩短［（12.5±3.2） d比（15.0±3.5） d，P=0.004］；术后中位住院天数明显缩短（7.5 d 比 9.0 d，P=0.006）；首次排气时间明显缩短（P=0.003）。中位随访时间58个月（13~129个月），期间未出现与肿瘤相关的死亡病例。开腹组有2例死亡，分别因乳腺癌和心脏病；腹腔镜组有1例死亡，死亡原因与胃间质瘤无关。72例患者中，40例术后接受伊马替尼辅助治疗，开腹组22例（50.0%），腹腔镜组18例（64.3%），两组接受伊马替尼辅助治疗的患者例数占比差异无统计学意义（χ2=1.414，P=0.234）。术后使用伊马替尼辅助治疗组总体生存率与未使用伊马替尼辅助治疗组相比差异有统计学意义 （P=0.015）。结论　与开腹手术相比，腹腔镜治疗长径在5~10 cm的中危胃间质瘤是一种安全有效的方法。实现R0切除的长径在5~10 cm的中危胃间质瘤患者术后使用伊马替尼辅助治疗未增加生存率，且未使用伊马替尼者未出现与肿瘤相关的死亡、复发及转移。     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

Antitumor Activity of Choerospondias axillaris Fruit Extract by Regulating the Expression of SNCAIP and SNCA on MDA-MB-231 Cells

Objective: Cancer is a huge problem of disease globally. Today, the percentage of people die from cancer is more than a combination of various diseases. In females, most common types of malignancies that occur are breast and cervical. The present focus has been shifted on medicinal plants as a form of therapy and there is a constant need to identify new therapeutic agents. Choerospondias axillaris (C. axillaris), an underutilized fruit, has been used in the remedy of various diseases. In the present communication, we evaluated the molecular mechanism of C. axillaris methanol extract in regulating cell death in human breast cancer cells (MDA-MB-231). Methods: Methanol extract of C. axillaris was prepared and compounds were screened by Gas chromatography-mass spectrometry. The effect of fruit extract was determined on MDA-MB-231 cells by MTT ((3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and to analyse the molecular mechanism of human breast cancer cells after treating with fruit extract, protein profiling study was performed by two-dimensional gel electrophoresis. Results: A total 9 differentially expressed proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS/MS) analysis. Among 9 identified proteins, synphilin-1 protein was found to be significantly downregulated, validated by western blot and RT-qPCR analysis. Possible interacting partners of synphilin-1 (SNCAIP) were analyzed for their possible role in cancer by the in-silico method. Conclusion: Our data implicate that the presence of bioactive compound(s) in C. axillaris fruits might play an important role in inhibiting the proliferation of breast carcinoma cells and Synphilin-1 protein may play a role of apoptotic function.     

Bacterial and fungal co-infection is a major barrier in COVID-19 patients: A specific management and therapeutic strategy is required

Microbial co-infections are another primary concern in patients with coronavirus disease 2019 (COVID-19), yet it is an untouched area among researchers. Preliminary data and systematic reviews only show the type of pathogens responsible for that, but its pathophysiology is still unknown. Studies show that these microbial co-infections are hospital-acquired/nosocomial infections, and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it. Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response, with lower CD4⁺ T and CD8⁺ T cell counts, indicating vulnerability to various co-infections. Despite this, there are only a few studies that recommend the management of co-infections.     

Quantitative Assessment and Predicting the Effects of Soil Pollutants on Herbaceous Biomass Production in Reserved Forests

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Heavy metal concentrations in surface soils of Reserved Forests (RFs) have a significant impact on...     

Diagnostic difficulty,delayed diagnosis,and increased tendencies of surgical treatment in fibromyalgia syndrome

Clinical Rheumatology - Aimed to evaluate the time elapsed between the onset of early symptoms and the diagnosis of fibromyalgia syndrome (FMS), the delays in diagnosis and frequent physician...     

Education Outcomes of Children Born Late Preterm: A Retrospective Whole-Population Cohort Study

Maternal and Child Health Journal - Early life exposures can have an impact on a child’s developmental trajectory and children born late preterm (34–36 weeks gestational age)...