Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Introduction: Carpal tunnel syndrome (CTS) is the commonest median nerve entrapment neuropathy of the hand, up to 90% of all nerve compression syndromes. The disease is often treated with conservative measures or surgery. The senior author initially intended to treat his own neurosurgical patients concurrently diagnosed with carpal tunnel syndrome in 2014, subsequently, he began to pick up more referrals from the primary healthcare group over the years. This has led to the setup of a peripheral and spine clinic to act as a hub of referrals. Objective: Department of Neurosurgery Sarawak aimed to evaluate the surgical outcome of carpal tunnel release done over five years. Methods: The carpal tunnel surgeries were done under local anaesthesia (LA) given by neurosurgeons (Bupivacaine 0.5% or Lignocaine 2%). Monitored anaesthesia care (MAC) was later introduced by our hospital neuroanaesthetist in the beginning of 2018 (Target-controlled infusion propofol and boluses of fentanyl). We looked into our first 17 cases and compared these to the two anaesthesia techniques (LA versus MAC + LA) in terms of patient’s pain score based on visual analogue scale (VAS). Results: Result showed MAC provided excellent pain control during and immediately after the surgery. None experienced anaesthesia complications. There was no difference in pain control at post-operation one month. Both techniques had equal good clinical outcome during patients’ clinic follow up. Conclusion: Neurosurgeons provide alternative route for CTS patients to receive surgical treatment. Being a designated pain free hospital, anaesthetist collaboration in carpal tunnel surgery is an added value and improves patients overall experience and satisfaction.

BACKGROUND: NUP98 has numerous partner genes of which plant homeodomain (PHD) finger protein 23 (PHF23) fusion with NUP98 (NP23) can be detected by RT-PCR in patients with cytogenetically normal acute myelogenous leukemia (AML). In this fusion transcript of NP23 PHD of PHF23 is known to specifically bind H3K4me3 residues and act as a chromatic modifier. Disulfiram (DSF) which inhibits the binding of PHD to H3K4me3 residues selectively killed NP23 myeloblasts in vitro and therefore, we planned to evaluate the efficacy of DSF in vivo. METHODS: Cultured 961C cells (CD45.2), NP23 myeloblast cells were transplanted into B57BL/6 mice (CD45.1). Using limit dilution assay the number of leukemic stem cells (LSCs) could be calculated. A certain amount of 961C cells were transplanted into B57BL/6 mice and DSF was treated after 1 week. The engraftment level was monitored with CD45.2. Kaplan Meier survival curve was used to compare the survival between therapeutic and control group. RESULTS: 961C cells could be transplanted without radiation in recipient mice. Calculated LSC was estimated to be 1 out of 184 cells (95% CI range, 56–609). When treated with DSF of different doses and administration routes in 961C recipient mice no survival advantage of DSF was observed in 961C transplanted immunocompetent mouse, however it was evident that engraftment level was consistent in both groups. CONCLUSION: No survival advantage of DSF in 961C transplanted immunocompetent mouse was observed, however it was evident that 961C cells shared niche with normal hematopoietic stem cells (HSCs). We expect that 961C cells and transplanted recipient mice have the potential to be used as in vivo system for new drugs development as well as for research dealing with niche for normal HSCs and LSCs.
Animals ; Disulfiram ; Fingers ; Granulocyte Precursor Cells ; Hematopoietic Stem Cells* ; Humans ; In Vitro Techniques ; Leukemia, Myeloid, Acute ; Mice ; Plants ; Stem Cells

The purpose of the current report is to present 6-year long-term stability and 10-year follow-up data for an adult patient who was treated with a tongue elevator for relapsed anterior open-bite. The 19-year-old male patient presented with the chief complaint of difficulty in chewing his food. Collectively, clinical and radiographic examinations revealed an anterior open-bite, low tongue posture, and tongue-tie. The patient opted for orthodontic treatment alone, without any surgical procedure. A lingual frenectomy was recommended to avoid the risk of relapse, but the patient declined because he was not experiencing tongue discomfort. Initial treatment of the anterior open-bite with molar intrusion and tongue exercises was successful, but relapse occurred during the retention period. A tongue elevator was used for retreatment, because the approach was minimally invasive and suited the patient's requirements regarding discomfort, cost, and time. The appliance changed the tongue posture and generated an altered tongue force, which ultimately resulted in intrusive dentoalveolar effects, and a subsequent counterclockwise rotation of the mandible. The results showed long-term stability and were maintained for six years through continual use of the tongue elevator. The results of this case indicated that a tongue elevator could be used not only as an alternative treatment for open-bite, but also as an active retainer.
Adult ; Elevators and Escalators ; Exercise ; Follow-Up Studies* ; Humans ; Male ; Mandible ; Mastication ; Molar ; Posture* ; Recurrence ; Retreatment ; Tongue* ; Young Adult

An association between inflammatory processes and the pathogenesis of insulin resistance has been increasingly suggested. The IkappaB kinase-beta (IKK-beta)/ nuclear factor-kappaB (NF-kappaB) pathway is a molecular mediator of insulin resistance. S-Adenosyl-L-methionine (SAM) has both antioxidative and anti-inflammatory properties. We investigated the effects of SAM on the glucose transport and insulin signaling impaired by the tumor necrosis factor alpha (TNFalpha) in 3T3-L1 adipocytes. SAM partially reversed the basal and insulin stimulated glucose transport, which was impaired by TNFalpha. The TNFalpha-induced suppression of the tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and Akt in 3T3-L1 adipocytes was also reversed by SAM. In addition, SAM significantly attenuated the TNFalpha-induced degradation of IkappaB-alpha and NF-kappaB activation. Interestingly, SAM directly inhibited the kinase activity of IKK-beta in vitro. These results suggest that SAM can alleviate TNFalpha mediated-insulin resistance by inhibiting the IKK-beta/NF-kappaB pathway and thus can have a beneficial role in the treatment of type 2 diabetes mellitus.

OBJECTIVE: Botulinum Toxin A (BoNT-A) is one of the therapeutic methods for the spastic decrement of the upper limb which appears from the patient after stroke. Decrement of stiffness is announced from many studies, but the effect of functional improvement was few examined closely so far clearly. The purpose of this study is to evaluate the effects of BoNT-A for the improvement of upper limb function in post stroke spastic hemiplegia. METHOD: Eleven chronic stroke patients (mean age 44.4 years) were included and injected BoNT-A (Dysport®, Ipsen, UK) according to degree of stiffness of each individual. Motor assessment scale, Box and Block test, Peg board test, Ashworth Scale, manual muscle test, Visual analogue scale, and subject satisfaction were applied at the baseline, and 1 week, 1, 2 and 3 months after interventions. All subjects were also submitted to ongoing rehabilitation therapy. RESULTS: Motor assessment scale results were statistically significant improvements at 1, 2 and 3 months after intervention (p<0.05). Also, statistically significant decreases in muscle tone as determined by the Ashworth scale were found at 1 week, 1, 2 and 3 months after injections (p<0.05). CONCLUSION: Botulinum Toxin A could derive the functional improvements as well as the tone reduction of upper limb in post stroke spastic hemiplegia.

OBJECTIVETo investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer's disease (AD).

METHODSMale Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin (1.5 mg/kg) on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde (MDA), glutathione reductase (GR) and reduced glutathione (GSH) levels in hippocampus and histopathology of hippocampal neurons.

RESULTSThe MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract (3.0 g/kg).

CONCLUSIONR. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.

Animals ; Behavior, Animal ; drug effects ; Biomarkers ; metabolism ; Cell Count ; Cognition Disorders ; chemically induced ; drug therapy ; physiopathology ; Hippocampus ; drug effects ; pathology ; Injections, Intraventricular ; Male ; Neurons ; drug effects ; pathology ; Neuroprotective Agents ; pharmacology ; Oxidative Stress ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Rhodiola ; metabolism ; Streptozocin ; administration & dosage ; Swimming ; physiology

BACKGROUNDThere are studies suggesting smoking may increase the risk of type 2 diabetes. Effects of smoking on insulin secretion and insulin resistance (IR) are, however, controversial.

METHODSThis is a cross-sectional study. Since there were very few smokers among Hong Kong Chinese women, only men (n = 1068) were analyzed in this report. Fasting and 2-hour plasma glucose and insulin were measured. Insulinogenic index as well as beta-cell function and IR based on homeostatic model assessment (HOMA) by computer model (HOMA Calculator v2.2) were calculated.

RESULTSOf the 1068 men, 147 had newly diagnosed diabetes, 131 newly diagnosed impaired glucose tolerance (IGT) and 790 were non-diabetic normal controls. Smokers had similar fasting and 2-hour insulin levels, insulinogenic index and HOMA derived beta-cell function as compared to non-smokers in the groups with diabetes, IGT or normal oral glucose tolerance test (OGTT). IR was also similar between smokers, ex-smokers and non-smokers in those with normal OGTT. In men with IGT or diabetes, after adjustment for age and body mass index, smokers were more insulin resistant as compared to non-smokers (IR, IGT: 1.59 +/- 1.07 vs 1.03 +/- 0.54, P < 0.05; diabetes: 1.96 +/- 1.36 vs 1.06 +/- 0.45, P < 0.01). With Logistic regression analysis, comparing smokers and non-smokers, IR was independently associated with smoking (odds ratio (95% CI), IGT: 2.23 (1.05, 4.71); diabetes: 3.92 (1.22, 12.58)). None of the other insulin parameters enter into the model among those with normal OGTT or comparing ex-smokers and non-smoker or smokers and ex-smokers.

CONCLUSIONSIn Chinese men, smoking did not show any direct association with insulin levels and pancreatic insulin secretion. Smoking men with IGT or diabetes appeared more insulin resistant than their non-smoking counterparts.

Adult ; Female ; Glucose Intolerance ; metabolism ; Humans ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; secretion ; Male ; Middle Aged ; Smoking ; metabolism

OBJECTIVE: To determine the relationship between cognitive-perceptual function and functional independence in stroke patients. METHOD: Thirty-three patients (16 male, 17 female) with first ever ischemic stroke were enrolled. Their mean age was 60.4 years and the mean post-onset duration was 8.1 months. Subjects underwent detailed cognitive assessment including digit span test, line bisection test, Albert test, Wechsler nonverbal memory scale, Korean Hopkins verbal learning Test, Rey complex figure test, and trail making test A. Their functional outcomes were assessed using Functional Independence Measure (FIM) and Modified Barthel Index (MBI). RESULTS: Among the cognitive subtests, Wechsler nonverbal memory scale, Albert test, and Rey complex figure test scores had significant correlation with both FIM and MBI scores. Patients with right hemispheric stroke showed significantly lower scores in line bisection test and Rey complex figure test than those with left hemispheric stroke patients. CONCLUSION: Visuospatial perception and nonverbal memory functions seemed to be two most important cognitive- perceptual domains for functional recovery of stroke patients.
Humans ; Male ; Memory ; Stroke* ; Trail Making Test ; Verbal Learning

AIM: To investigate the effects of milrinone (a selective phosphdiesterase III inhibitor PDE 3) on insulin secretion, blood glucose, plasma free fatty acids (FFA) and dose-response relationship, and assess possible effects of milrinone on glucose metabolism and insulin sensitivity in conscious rats. METHODS: The catheterized nonstressed rats were administered by the varying doses of milrinone (1, 5, 25 ?mol/kg) and were compared with controls. A hyperinsulinaemic- euglycaemic clamp was established in awake rats, and milrinone(25 ?mol/kg) and 25% dimethyl sulfoxide (DMSO, as a control) were given at 120 min during hyperinsulinaemic- euglycaemic clamp. Glucose turnover was decided by gas chromatograph mass spectrometer (GC-MS). RESULTS: After dosing, plasma FFA levels in 3 milrinone groups significantly increased compared with the controls and before dosing. The percentages of elevation of FFA by the different milrinone doses were very similar, 50%, 52%, 55% for 1, 5, 25 ?mol/kg respectively at 2 min after dosing. Plasma insulin levels were significantly elevated in the 5 and 25 ?mol/kg groups, and the effect of milrinone on glucose concentration was detectable only 25 ?mol/kg group. During hyperinsulinaemic clamp, there were significant increase in plasma FFA (from 173.1?15 2 to 633 8?87 3 ?Eq/L) and hepatic glucose production (HGP), and a significant decrease in glucose infusion rates (GIR) (to about 21%). CONCLUSION: These data suggest that milrinone impaires the abilities of insulin to suppress lipolysis and HGP, and insulin-mediated glucose utilization in peripheral tissue. Therefore, milrinone administration may induce an acute insulin resistance in vivo.