Targeting DNA damage repair mechanism by using RAD50-silencing siRNA nanoparticles to enhance radiotherapy in triple negative breast cancer.

Radiotherapy (RT) is one of major therapeutic modalities in combating breast cancer. In RT, ionizing radiation is employed to induce DNA double-strand breaks (DSBs) as a primary mechanism that causes cancer cell death. However, the induced DNA damage can also trigger the activation of DNA repair mechanisms, reducing the efficacy of RT treatment.

Biocompatible and bioactivable terpolymer-lipid-MnO Nanoparticle-based MRI contrast agent for improving tumor detection and delineation.

Early and precise detection of solid tumor cancers is critical for improving therapeutic outcomes. In this regard, magnetic resonance imaging (MRI) has become a useful tool for tumor diagnosis and image-guided therapy. However, its effectiveness is limited by the shortcomings of clinically available gadolinium-based contrast agents (GBCAs), i.

High regeneration may not contribute to the forest's carbon storage: a case study in the mangrove forest of Rajang-Belawai-Paloh delta, Sarawak.

The alarming rate of the mangrove ecosystem loss poses a threat of losing valuable carbon sinks. This study was conducted to (i) determine the growth structure in different vegetation types and (ii) compare the aboveground biomass (AGB) and carbon storage in different vegetation types. The study was conducted at four vegetation types within the Rajang-Belawai-Paloh delta i.

Remodeling Tumor Immune Microenvironment by Using Polymer-Lipid-Manganese Dioxide Nanoparticles with Radiation Therapy to Boost Immune Response of Castration-Resistant Prostate Cancer.

Despite substantial progress in the treatment of castration-resistant prostate cancer (CRPC), including radiation therapy and immunotherapy alone or in combination, the response to treatment remains poor due to the hypoxic and immunosuppressive nature of the tumor microenvironment. Herein, we exploited the bioreactivity of novel polymer-lipid manganese dioxide nanoparticles (PLMDs) to remodel the tumor immune microenvironment (TIME) by increasing the local oxygen levels and extracellular pH and enhancing radiation-induced immunogenic cell death. This study demonstrated that PLMD treatment sensitized hypoxic human and murine CRPC cells to radiation, significantly increasing radiation-induced DNA double-strand breaks and ultimately cell death, which enhanced the secretion of damage-associated molecular patterns, attributable to the induction of autophagy and endoplasmic reticulum stress.

Advances in Nanomedicine Design: Multidisciplinary Strategies for Unmet Medical Needs.

Globally, a rising burden of complex diseases takes a heavy toll on human lives and poses substantial clinical and economic challenges. This review covers nanomedicine and nanotechnology-enabled advanced drug delivery systems (DDS) designed to address various unmet medical needs. Key nanomedicine and DDSs, currently employed in the clinic to tackle some of these diseases, are discussed focusing on their versatility in diagnostics, anticancer therapy, and diabetes management.

Comparison of continuous preperitoneal infiltration versus patient controlled analgesia for pain control in elective colorectal surgery.

Background: Post-operative analgesia is crucial in enhanced recovery after surgery and to minimize post-operative complications. There remains data paucity on the efficacy of preperitoneal analgesia (PPA) compared to patient-controlled analgesia (PCA). This study aims to examine the efficacy of preperitoneal infusion as analgesia following elective colorectal surgery.

Outcomes of traumatic extremity vascular injuries from a Malaysian level 1 trauma center.

Background: In Malaysia, management of traumatic vascular injuries is at the discretion of the treating surgeon (trauma or vascular surgery). This study was conducted to report on the epidemiology, mechanism of injury and outcomes of vascular injuries managed in a regional level 1 trauma center.

Methods: This is a retrospective cohort study of all patients treated for traumatic extremity vascular injuries from January 2018 to December 2020.

Redox-responsive nanoparticles enhance radiation therapy by altering multifaceted radio-resistance mechanisms in human castration-resistant prostate cancer cells and xenografts.

Introduction: Radiation therapy (RT) is a major modality for the treatment of prostate cancer (PCa), especially castration-resistant PCa (CRPC). However, hypoxia, often seen in PCa tumors, leads to radiation-resistance. This work investigates the effect of a novel oxygen-generating polymer-lipid manganese dioxide nanoparticle (PLMDs) on improving RT outcomes in CRPC xenograft models by modulating the tumor microenvironment (TME) both before and after RT.

Pharmaceutical nanoformulation strategies to spatiotemporally manipulate oxidative stress for improving cancer therapies - exemplified by polyunsaturated fatty acids and other ROS-modulating agents.

Chronic oxidative stress and inflammation promote tumorigenesis and tumor progression, while certain chemotherapeutic drugs and radiation are applied to produce free radicals against cancer cells. To reduce tumor-promoting oxidative stress and protect normal tissue from chemotherapy and radiation-associated toxicity, dietary antioxidants, such as omega-3 polyunsaturated fatty acids (PUFA), have been combined with cancer therapies. However, the results of clinical studies are mixed with little to no benefit to therapeutic effect, and even exacerbated adverse effects.

Predictors of Mortality and Outcomes of Ventilated Patients Managed in a Resource-Limited Acute Surgical Ward.

Background: Acute care surgery is an important component of health care in the developed nations. However, in Malaysia, acute care surgery is yet to be recognized as a specific subspecialty service. Due to high demands of limited ICU beds, some patients have to be ventilated in the wards.

Intrauterine contraceptive device embedded in bladder wall with calculus formation removed successfully with open surgery.

An Intrauterine contraceptive devices (IUCD) is commonly inserted by the primary health care physician. It can migrate into pelvic or abdominal organs. When a pregnancy occurs following an insertion of an IUCD, there should be a high suspicion of uterine perforation or possible migration.

Older age and duration of exposure to type 2 diabetes in selective screening of asymptomatic carotid artery stenosis for primary stroke prevention-A single institution experience.

Aims: To evaluate the incidence and risk factors for carotid artery stenosis amongst asymptomatic type 2 diabetes from a single Malaysian tertiary institution.

Methods: This is a prospective cross-sectional study of asymptomatic type 2 diabetics selected from the outpatient ophthalmology and endocrine clinics for carotid duplex ultrasound scanning performed by a single radiologist. The duplex ultrasound criteria were based on the North American Symptomatic Carotid Endarterectomy Trial (NASCET) classification of carotid artery stenosis.

Multitargeted Nanoparticles Deliver Synergistic Drugs across the Blood-Brain Barrier to Brain Metastases of Triple Negative Breast Cancer Cells and Tumor-Associated Macrophages.

Patients with brain metastases of triple negative breast cancer (TNBC) have a poor prognosis owing to the lack of targeted therapies, the aggressive nature of TNBC, and the presence of the blood-brain barrier (BBB) that blocks penetration of most drugs. Additionally, infiltration of tumor-associated macrophages (TAMs) promotes tumor progression. Here, a terpolymer-lipid hybrid nanoparticle (TPLN) system is designed with multiple targeting moieties to first undergo synchronized BBB crossing and then actively target TNBC cells and TAMs in microlesions of brain metastases.

Clinical Audit of Urosepsis Treated in a Malaysian Surgery Unit.

This is a retrospective audit of all patients admitted to the surgical unit for urosepsis from June 2014 to June 2015 at the General Surgery Unit of Hospital Sultan Ismail, Malaysia. Demographics, comorbidities, presenting symptoms, length of stay (LOS), mortality, and associated risk factors were recorded. There were 35 patients treated for urosepsis with a male preponderance of 21/35 patients.

A rare presentation of chronic myeloid leukaemia with priapism treated with corporoglandular shunting.

Priapism is a rare clinical presentation of a patient with chronic myeloid leukaemia (CML). Herein, we present a young Nepalese man that presented to the emergency department with an acute and painful penile erection for two days. Clinically, he was pale and abdominal examination revealed hepatomegaly.

Combining Tumor Microenvironment Modulating Nanoparticles with Doxorubicin to Enhance Chemotherapeutic Efficacy and Boost Antitumor Immunity.

Background: Tumor microenvironment (TME) and associated multiple factors are found to contribute to the failures in cancer therapies, including chemo- and immunotherapy. Here we report a new multimodal strategy that uses a bioreactive multifunctional hybrid polymer-lipid encapsulated manganese dioxide nanoparticle (PLMD NP) system to remodel the TME, suppress drug resistance factors, reverse immunosuppressive conditions, and enhance chemotherapy efficacy.

Methods: The influence of PLMD NPs on enhancing cellular uptake in EMT6 mouse breast cancer cells and tumor penetration of doxorubicin (DOX) in EMT6 orthotopic breast tumor mouse model was evaluated using confocal microscopy (n = 3-4).

Pulmonary artery catheter entrapment after mitral valve surgery and the use of transesophageal echocardiography to accurately determine the site of entrapment.

The prevalence of pulmonary artery catheter (PAC) entrapment in open-heart surgery is scarce with a prevalence rate of 0.065%. Challenges in managing such cases lie particularly in choosing the modalities (chest roentgenogram, fluoroscopy, and transesophageal echocardiography) to accurately identify the anatomic location and cause of entrapment.

A Rare Presentation of Anterior Mediastinal Teratoma Mimicking Valvular Heart Disease with A Systolic Murmur.

Extrinsic pulmonary artery stenosis caused by anterior mediastinum teratoma presenting with an ejection systolic murmur is a rare phenomenon. Till date, 15 cases have been reported (inclusive of this case) in the English literatures. Herein we report a 20 year old female with extrinsic pulmonary artery stenosis because of compression by an anterior mediastinal teratoma with a loud ejection systolic murmur.

Major tracheobronchial injuries: Management of two rare cases.

Tracheobronchial injuries are uncommon and a high level of suspicion is needed for immediate diagnosis and prompt treatment. In this case series, two rare cases of tracheobronchial injuries is described showing variable clinical presentations with different levels of injury. Our first case was seen in a 20 years old male whom had a direct impact on the neck and presented with upper tracheal injury.

Prognostic predictors of early mortality from exsanguination in adult trauma: a Malaysian trauma center experience.

Background: Trauma mortality due to exsanguination is the second most common cause of death. The objective of this study is to investigate the predictors for early death from exsanguination.

Methods: A prognostic study was done to identify predictors of early mortality due to exsanguination.

Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy - an illustration with firsthand examples.

Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention.

Case report of a high voltage electrical injury and review of the indications for early fasciotomy in limb salvage of an electrically injured limb.

Electrical injuries make up a relatively small portion of burn injuries. Safety measures in place on domestic electricity supply have reduced the occurrence of high voltage electrical injuries. We present the case of a young man who sustained a high voltage electrical injury on all four limbs.