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Previous studies comparing outcomes of hepatocellular carcinoma (HCC) patients after living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) showed conflicting results, and most studies measured survival outcomes from the time of liver transplantation (LT). This retrospective study was aimed to evaluate the long-term outcomes of HCC patients listed for LT using intention-to-treat (ITT) and propensity score matching (PSM) analyses. Clinicopathological data were retrieved from a prospectively collected database. From 1995 to 2014, 375 HCC patients were listed for LT. ITT-LDLT group had 188 patients, whereas ITT-DDLT group had 187 patients. Twenty-seven patients (14.4%) and 122 patients (65.2%) were delisted from LDLT and DDLT waitlist, respectively. The 1-, 3- and 5-year overall survival rates were significantly better in ITT-LDLT group than ITT-DDLT group (94.1 vs. 77.5%, 81.4 vs. 48.7% and 75.9 vs. 40.8%). High alphafetoprotein (AFP) and ITT-DDLT treatment arm were independent poor prognostic factors affecting overall survival. LDLT group (n = 161) had more young patients, poorer liver function, higher AFP, more tumors outside Milan/UCSF criteria, when compared with DDLT group (n = 85). After PSM, the 1-, 3- and 5-year overall (95.4 vs. 98.5%, 80.0 vs. 92.3% and 73.4 vs. 84.4%) and recurrence-free (87.7% vs. 90.8%, 76.9% vs. 83.1% and 72.2% vs. 81.5%) survival rates were comparable between the matched LDLT and the matched DDLT group, respectively. Survival benefit of LDLT was observed for HCC patients with ITT analysis. Despite a more advanced tumor stage, overall and recurrence-free survival rates were comparable between LDLT and DDLT using PSM analysis.

Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination and, in some instances, skin testing and graded challenges. Induction of drug tolerance procedures may also be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a background on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such as penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid and non-steroidal anti-inflammatory drugs, and therapeutic monoclonal antibodies.

Plants have evolved to protect leaf mesophyll tissue from damage caused by UV-B radiation by producing an array of UV-absorbing secondary metabolites. Flavonoids (phenolic glycosides) and sinapate esters (hydroxycinnamates) have been implicated as UV-B protective compounds because of the accumulation in the leaf epidermis and the strong absorption in the wavelengths corresponding to UV. Environmental adaptations by plants also generate a suite of responses for protection against damage caused by UV-B radiation, with plants from high elevations or low latitudes generally displaying greater adaptation or tolerance to UV-B radiation. In an effort to explore the relationships between plant lignin levels and composition, the origin of growth elevation, and the hierarchical synthesis of UV-screening compounds, a collection of natural variants as well as transgenic Populus spp. were examined for sensitivity or acclimation to UV-B radiation under greenhouse and laboratory conditions. Noninvasive, ecophysiological measurements using epidermal transmittance and chlorophyll fluorescence as well as metabolite measurements using UPLC-MS generally revealed that the synthesis of anthocyanins, flavonoids, and lignin precursors are increased in Populus upon moderate to high UV-B treatment. However, poplar plants with genetic modifications that affect lignin biosynthesis, or natural variants with altered lignin levels and compositions, displayed complex changes in phenylpropanoid metabolites. A balance between elevated metabolic precursors to protective phenylpropanoids and increased biosynthesis of these anthocyanins, flavonoids, and lignin is proposed to play a role in the acclimation of Populus to UV-B radiation and may provide a useful tool in engineering plants as improved bioenergy feedstocks.

Comprehensive characterizations of bladder cancer (BCa) have established molecular phenotype classes with distinct alterations and survival trends. Extending these studies within the tyrosine kinase (TK) family to identify disease drivers could improve our use of TK inhibitors to treat specific patient groups or individuals. We examined the expression distribution of TKs as a class (n = 89) in The Cancer Genome Atlas (TCGA) muscle invasive BCa data set (n >400). Patient profiles of potentially oncogenic alterations (overexpression and/or amplification) clustered TKs into 3 groups; alterations of group 1 and 3 TKs were associated with significantly worse patient survival relative to those without alterations. Many TK pathways induce epithelial-to-mesenchymal transition (EMT), which promotes tumor invasiveness and metastasis. Overexpression and/or amplification among 9 EMT transcriptional activators occurred in 43% of TCGA cases. Co-occurring alterations of TKs and EMT transcriptional activators involved most group 1 TKs; 24% of these events were associated with significantly worse patient survival. Co-occurring alterations of receptor TKs and their cognate ligands occurred in 16% of TCGA cases and several BCa-derived cell lines. Suppression of GAS6, MST1 or CSF1, or their respective receptors (AXL, MST1R and CSF1R), in BCa cell lines was associated with decreased receptor activation, cell migration, cell proliferation and anchorage independent cell growth. These studies reveal the patterns and prevalence of potentially oncogenic TK pathway-related alterations in BCa and identify specific alterations associated with reduced BCa patient survival. Detection of these features in BCa patients could better inform TK inhibitor use and improve clinical outcomes.

After reconstruction, the return to full competition rate of athletes is low, while the re-injury rate remains high despite the completion of a rehabilitation programme. Primary ACL prevention programmes are well developed, yet few research papers focus on secondary ACL injury prevention. The aim of current review is to determine if current ACL secondary prevention training has a positive influence on the re-injury rate, the clinical or functional outcomes, or the risk of re-injury in athletes. Studies investigating secondary prevention of ACL were searched in PubMed and EBSCOhost, followed by a review of the references in the identified articles. The existing evidence suggests that neuromuscular training, eccentric strengthening, and plyometric exercises may have a potential impact on improving biomechanical, functional, and psychological outcomes in athletes; however, the studies on the prevention of second ACL injury in athletes is scarce and inconclusive. Future research is needed to investigate the effectiveness of secondary ACL prevention in reducing the re-injury rates. (PROSPERO Registration number: CRD42021291308).

The vast majority of individuals labelled as allergic are not deemed truly allergic upon appropriate assessment by an allergist. A label of beta-lactam allergy carries important risks for individual and public health. This article provides an overview of beta-lactam allergy, implications of erroneous beta-lactam allergy labels and the impact that can be provided by structured allergy assessment. We provide recommendations on how to stratify risk of beta-lactam allergy, beta lactam challenge protocols as well as management of patients at high risk of beta-lactam allergy.

Efficient approaches for the precise genetic engineering of human pluripotent stem cells (hPSCs) can enhance both basic and applied stem cell research. Adeno- associated virus (AAV) vectors are of particular interest for their capacity to mediate efficient gene delivery to and gene targeting in various cells. However, natural AAV serotypes offer only modest transduction of human embryonic and induced pluripotent stem cells (hESCs and hiPSCs), which limits their utility for efficiently manipulating the hPSC genome. Directed evolution is a powerful means to generate viral vectors with novel capabilities, and we have applied this approach to create a novel AAV variant with high gene delivery efficiencies (~50%) to hPSCs, which are importantly accompanied by a considerable increase in gene-targeting frequencies, up to 0.12%. While this level is likely sufficient for numerous applications, we also show that the gene-targeting efficiency mediated by an evolved AAV variant can be further enhanced (>1%) in the presence of targeted double- stranded breaks (DSBs) generated by the co-delivery of artificial zinc finger nucleases (ZFNs). Thus, this study demonstrates that under appropriate selective pressures, AAV vectors can be created to mediate efficient gene targeting in hPSCs, alone or in the presence of ZFN- mediated double-stranded DNA breaks.

Background and Objectives: Although chronic low back pain (CLBP) is known to negatively affect multiple aspects of the lives of older people, prior qualitative studies mainly focused on the lived experiences of older people with CLBP in Western countries. Given cultural and contextual differences and poor understanding of CLBP in older women with CLBP, it is important to better understand the concerns and lived experiences of Chinese older women with CLBP. The current study aimed to investigate the experiences, challenges, concerns, and coping strategies of older women with CLBP in Hong Kong. Research Design and Methods: A total of 15 community-dwelling older women with CLBP aged ≥60 years were recruited from a physiotherapy clinic or a community center for semi-structured interviews. The interviews were audio recorded and transcribed ‘verbatim’. The transcription was imported to NVivo 12 software. Thematic analysis was conducted using Braun and Clarke’s method. Results: Five themes were identified: (1) physical impacts of CLBP on daily life; (2) psychological influences of CLBP; (3) management of CLBP; (4) family support; and (5) social activities and support. Discussion and implications: Negative physical and psychosocial impacts of CLBP were common among older women, and they adopted diverse pain management strategies, although some of their treatment options were influenced by the Chinese culture. Misbeliefs and responses of family and friends also affected their management strategies. Elderly community centers are a significant source of social support for older women with CLBP, making it an ideal platform for establishing self-help groups to facilitate their self-management of CLBP.