Adolescent ; Adult ; Aged ; Aged, 80 and over ; Emergency Service, Hospital ; Female ; Humans ; Male ; Middle Aged ; Singapore ; Skin Diseases ; diagnosis ; Tertiary Care Centers ; Young Adult

INTRODUCTIONCutaneous melanoma is rare in Asia and the clinical presentation and outcome of melanoma is not well described in Southeast Asia. In addition, it is unclear if ethnic variations exist between the various racial groups. The objective of our study is to present the clinical characteristics of melanoma in Singapore and to highlight ethnical differences between Asians and Caucasians living in Singapore.

MATERIALS AND METHODSData were retrospectively collected from 48 patients with histological confirmation of melanoma who were seen in both the National Skin Centre and National Cancer Centre of Singapore.

RESULTSAcral lentiginous melanoma (ALM) was the most common subtype of melanoma in Singapore (50%). A higher proportion of non-ALM subtypes of melanoma compared to ALM were diagnosed at stage 1 (48% vs. 25%). The delay in diagnosis of ALM was 27 months compared to 12 months in other subtypes. Compared to Caucasians, there was a trend towards Asian patients being older, having a higher proportion of ALM and a longer delay to diagnosis.

CONCLUSIONGeographical and ethnic variations in the clinical presentation of melanoma exist. Specially adapted programmes are necessary to increase awareness of the different clinical presentation of melanoma in Asia and to encourage examination of the palms and soles in order to reduce the delay in diagnosis.

Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; European Continental Ancestry Group ; Female ; Humans ; Male ; Melanoma ; diagnosis ; epidemiology ; ethnology ; pathology ; Middle Aged ; Retrospective Studies ; Singapore ; epidemiology ; Skin Neoplasms ; diagnosis ; epidemiology ; ethnology ; pathology

Chemotherapy-induced cancer cell secretomes promote resistance due, in part, to a predominant glycolytic energy metabolism, which drives aggressive cancer cell proliferation. However, the characterization of these secretomes and the molecular events that associate them with acquired drug resistance remain poorly understood. In this study, we show that secretomes of cancer cells with high-level paclitaxel resistance stimulated cell proliferation and suppressed drug-induced apoptosis of drug-sensitive cells. We also found that drug (docetaxel)-stimulated induction of interferon-α (IFN-α), IFN-λ and tumor necrosis factor-α (TNF-α) release in drug-sensitive cells was lowered by these secretomes. The promotion of cell proliferation by paclitaxel-resistant (PacR) cancer cell secretomes was associated, in part, with an increase in S phase of the cell cycle and downregulation of the cell death pathway that supports escape from apoptosis. In addition, we also found that the regulation of targeted glycolysis in PacR cancer cells alters the effects of the secretomes on cell growth, apoptosis, ATP generation and acquired drug resistance. Further study revealed that the deletion of FOXO3a transcription exacerbates glycolytic shift-induced apoptosis by rescuing TRAIL expression. By generating a docetaxel–cross-resistant PacR cancer cell line (PacR/DCT), we further clarified the role of FOXO3a in glycolysis-associated mediation of P-glycoprotein/ABCB1 hyperactivity that induces docetaxel cross-resistance. These findings suggest that suppression of the cellular energy supply by targeting glycolysis may inhibit the multiplicity of acquired chemotherapy resistance. Therefore, the therapeutic inhibition of FOXO3a might direct glycolysis to induce apoptosis and overcome multidrug resistance in cancer cells.
Adenosine Triphosphate ; Apoptosis* ; Cell Cycle ; Cell Death ; Cell Line ; Cell Proliferation ; Down-Regulation ; Drug Resistance ; Drug Resistance, Multiple ; Drug Therapy ; Energy Metabolism ; Glycolysis ; Necrosis ; Negotiating ; Paclitaxel ; S Phase ; United Nations*

Primary care practitioners play an important role in administering and advocating vaccinations against vaccine-preventable infectious diseases and ensuring herd immunity in our population. This is a follow-up article to an earlier one which dealt with the principles of vaccine scheduling and administration. This article describes several false contraindications to vaccination that a primary care practitioner may encounter, including pregnancy, current breastfeeding, history of febrile seizures, and having immunosuppressed or pregnant household contacts. We aimed to provide a guide for safe and timely vaccine administration in the primary care setting.
Humans ; Primary Health Care ; standards ; Public Health ; Safety ; Vaccination ; methods ; standards

HIV/STIs remain a major global public health problem. One of the global strategies for the prevention and control of HIV/STIs is to interrupt their transmission, which requires the public health methods based on scientific evidence and cost-effectiveness. The scale-up of male circumcision services in the priority countries of the HIV-prevention project in sub-Saharan Africa has been hampered by the scarcity of trained providers and relative technical difficulty of male circumcision techniques recommended by WHO and UNAIDS. Shang Ring is an innovative and disposable device for male circumcision, which has been safely used for over 600 000 males in China since 2006. Clinical studies of more than 3 000 cases of Shang Ring circumcision in China, Kenya, Zambia, and Uganda have demonstrated its safety, effectiveness, acceptability and ease of use. The most obvious advantages of Shang Ring include short procedure time (3-6 min), excellent postoperative cosmesis, low rate of complications, high acceptance by clients and providers, ease of use, and standardization for reliable performance. As an innovative technique, Shang Ring has a great potential for facilitating the safe and effective scale-up of circumcision services. This article comprehensively reviews the clinical studies of Shang Ring male circumcision in China and Africa.
Africa ; China ; Circumcision, Male ; instrumentation ; methods ; HIV Infections ; prevention & control ; Humans ; Male

INTRODUCTIONThis study aimed to examine the long-term clinical outcomes of coronary fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) in a real-world population in an Asian tertiary centre.

MATERIALS AND METHODSAll patients who underwent FFR measurement for intermediate coronary lesions in our centre from June 2002 to December 2009 were enrolled. A threshold of FFR ≤0.75 was used for revascularisation. All the patients were prospectively followed-up for major adverse cardiac events (MACE) of death, myocardial infarction (MI), target vessel revascularisation (TVR) and stent thrombosis.

RESULTSBased on FFR measurement, 368 (57%) patients were treated medically while 278 (43%) underwent revascularisation. At a mean follow-up duration of 29.7 ± 16 months, 53 (14.4%) patients in the medical therapy group and 32 (11.5%) patients in the revascularised group experienced MACE (P = 0.282). There were no statistical differences in all the clinical endpoints between the 2 groups.

CONCLUSIONMedical therapy based on FFR measurement is associated with low incidences of MACE at long-term follow-up.

Adult ; Aged ; Aspirin ; therapeutic use ; Coronary Stenosis ; complications ; diagnosis ; therapy ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; methods ; Platelet Aggregation Inhibitors ; therapeutic use ; Retrospective Studies ; Ticlopidine ; analogs & derivatives ; therapeutic use ; Treatment Outcome

Methods: Patients undergoing posterior lumbar decompression (PLD) of ≤4 levels were divided into severe and non-severe central canal stenosis groups based on the Lee magnetic resonance imaging (MRI) grading system. Patients without preoperative MRI or inadequate visualization on radiographs were excluded. Surgical characteristics, clinical outcomes, and sagittal measurements were compared. Multivariate logistic regression was performed to determine the predictors of pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), and pelvic incidence minus lumbar lordosis (PI–LL). Results: Of the 142 patients included, 39 had severe stenosis, and 103 had non-severe stenosis. The mean follow-up duration for the cohort was 4.72 months. Patients with severe stenosis were older, had higher comorbidity indices and levels decompressed, and longer lengths of stay and operative times (p <0.001). Although those with severe stenosis had lower lordosis, lower SS, and higher PI–LL mismatch preoperatively, no differences in Delta LL, SS, PT, or PI–LL were observed between the two groups (p >0.05). On multivariate regression, severe stenosis was a significant predictor of a lower preoperative LL (estimate=−5.243, p =0.045) and a higher preoperative PI–LL mismatch (estimate=6.192, p =0.039). No differences in surgical or clinical outcomes were observed (p >0.05). Conclusion Severe central lumbar stenosis was associated with greater spinopelvic mismatch preoperatively. Sagittal balance improved in both patients with severe and non-severe stenosis after PLD to a similar degree, with differences in sagittal parameters remaining after surgery. We also found no differences in postoperative outcomes associated with stenosis severity.

It has been reported that long-term enhancement of superficial dorsal horn (DHs) excitatory synaptic transmission underlies central sensitization, secondary hyperalgesia, and persistent pain. We tested whether impaired clearance of K+ and glutamate by glia in DHs may contribute to initiation and maintenance of the CNS pain circuit and sensorimotor abnormalities. Transient exposure of the spinal cord slice to fluorocitrate (FC) is shown to be accompanied by a protracted decrease of the DHs optical response to repetitive electrical stimulation of the ipsilateral dorsal root, and by a similarly protracted increase in the postsynaptic response of the DHs like LTP. It also is shown that LTP(FC) does not occur in the presence of APV, and becomes progressively smaller as [K+]o in the perfusion solution decreased from 3.0 mM to 0.0 mM. Interestingly LTP(FC) is reduced by bath application of Bic. Whole-cell patch recordings were carried out to evaluate the effects of FC on the response of DHs neurons to puffer-applied GABA. The observations reveal that transient exposure to FC is reliably accompanied by a prolonged (>1 hr) depolarizing shift of the equilibrium potential for the DHs neuron transmembrane ionic currents evoked by GABA. Considered collectively, the findings demonstrate that LTP(FC) involves (1) elevation of [K+]o in the DHs, (2) NMDAR activation, and (3) conversion of the effect of GABA on DHs neurons from inhibition to excitation. It is proposed that a transient impairment of astrocyte energy production can trigger the cascade of dorsal horn mechanisms that underlies hyperalgesia and persistent pain.
Animals ; Astrocytes ; Baths ; Central Nervous System Sensitization ; Electric Stimulation ; gamma-Aminobutyric Acid* ; Glutamic Acid ; Horns ; Hyperalgesia ; Neuroglia ; Neurons ; Perfusion ; Posterior Horn Cells* ; Rats* ; Spinal Cord* ; Spinal Nerve Roots ; Synaptic Transmission

Regulation of cell volume is an important aspect of cellular homeostasis during neural activity. This volume regulation is thought to be mediated by activation of specific transporters, aquaporin, and volume regulated anion channels (VRAC). In cultured astrocytes, it was reported that swelling-induced mitogen-activated protein (MAP) kinase activation is required to open VRAC, which are thought to be important in regulatory volume decrease and in the response of CNS to trauma and excitotoxicity. It has been also described that sodium fluoride (NaF), a recognized G-protein activator and protein phosphatase inhibitor, leads to a significant MAP kinase activation in endothelial cells. However, NaF's effect in volume regulation in the brain is not known yet. Here, we investigated the mechanism of NaF-induced volume change in rat and mouse hippocampal slices using intrinsic optical signal (IOS) recording, in which we measured relative changes in intracellular and extracellular volume as changes in light transmittance through brain slices. We found that NaF (1~5 mM) application induced a reduction in light transmittance (decreased volume) in CA1 hippocampus, which was completely reversed by MAP kinase inhibitor U0126 (10 µM). We also observed that NaF-induced volume reduction was blocked by anion channel blockers, suggesting that NaF-induced volume reduction could be mediated by VRAC. Overall, our results propose a novel molecular mechanism of NaF-induced volume reduction via MAP kinase signaling pathway by activation of VRAC.
Animals ; Astrocytes ; Brain ; Cell Size ; Endothelial Cells ; Fluorides* ; GTP-Binding Proteins ; Hippocampus ; Homeostasis ; Mice ; Phosphotransferases* ; Rats ; Sodium Fluoride