Functional and molecular profiling of hematopoietic stem cells during regeneration.

Hematopoietic stem cells (HSCs) enable hematopoietic stem cell transplantation (HCT) through their ability to replenish the entire blood system. Proliferation of HSCs is linked to decreased reconstitution potential, and a precise regulation of actively dividing HSCs is thus essential to ensure long-term functionality. This regulation becomes important in the transplantation setting where HSCs undergo proliferation followed by a gradual transition to quiescence and homeostasis. Although mouse HSCs have been well studied under homeostatic conditions, the mechanisms regulating HSC activation under stress remain unclear. Here, we analyzed the different phases of regeneration after transplantation. We isolated bone marrow from mice at 8 time points after transplantation and examined the reconstitution dynamics and transcriptional profiles of stem and progenitor populations. We found that regenerating HSCs initially produced rapidly expanding progenitors and displayed distinct changes in fatty acid metabolism and glycolysis. Moreover, we observed molecular changes in cell cycle, MYC and mTOR signaling in both HSCs, and progenitor subsets. We used a decay rate model to fit the temporal transcription profiles of regenerating HSCs and identified genes with progressively decreased or increased expression after transplantation. These genes overlapped to a large extent with published gene sets associated with key aspects of HSC function, demonstrating the potential of this data set as a resource for identification of novel HSC regulators. Taken together, our study provides a detailed functional and molecular characterization of HSCs at different phases of regeneration and identifies a gene set associated with the transition from proliferation to quiescence.

[A time-series study on the association of ambient temperature with daily outpatient visits of eczema in Huizhou city].

Objective: To explore the impact of environmental temperature exposure on eczema visits. Methods: Eczema clinic data from January 1, 2016 to December 31, 2019 were collected from the Huizhou Dermatology Hospital, and data on meteorological factors (average daily temperature and relative humidity) for the same period were derived from 86 meteorological stations of the Guangdong Provincial Climate Center. A distributed lag nonlinear model (DLNM) was used to assess the lagged effect of environmental temperature exposure on eczema, and a natural smooth spline function was used to control the nonlinear confounding of humidity. Results: There were 254 053 eczema outpatient visits at the Huizhou Dermatology Hospital within four years, with an average of 173.89 visits per day. The relationship between daily average temperature and the number of visits was non-linear (U shape). The risk of eczema increased by 2.20% (1.19%-3.21%) for every 1 ℃ decrease for the low temperature, and increased by 2.35% (1.24%-3.5%) for every 1 ℃ increase for the high temperature. The effect of high temperature was greater than that of low temperature. In all cases, 1.60% (0.44%-2.68%) of eczema outpatient visits were attributed to low temperature and the attributable number was 4 065 (1 128-6 798), while 6.33% (1.40%-10.87%) of eczema outpatient visits were due to high temperature and the attributable number was 16 082 (3 557-27 616). Conclusion: Both high temperature and low temperature are associated with increased risk of eczema.

Schlafen2 is a regulator of quiescence in adult murine hematopoietic stem cells.

Even though hematopoietic stem cells (HSC) are characterized by their ability to self-renew and differentiate, they primarily reside in quiescence. Despite the immense importance of this quiescent state, its maintenance and regulation is still incompletely understood. Schlafen2 (Slfn2) is a cytoplasmic protein known to be involved in cell proliferation, differentiation, quiescence, interferon response, and regulation of the immune system. Interestingly, Slfn2 is highly expressed in primitive hematopoietic cells. In order to investigate the role of Slfn2 in the regulation of HSC we have studied HSC function in the elektra mouse model, where the elektra allele of the Slfn2 gene contains a point mutation causing loss of function of the Slfn2 protein. We found that homozygosity for the elektra allele caused a decrease of primitive hematopoietic compartments in murine bone marrow. We further found that transplantation of elektra bone marrow and purified HSC resulted in a significantly reduced regenerative capacity of HSC in competitive transplantation settings. Importantly, we found that a significantly higher fraction of elektra HSC (as compared to wild-type HSC) were actively cycling, suggesting that the mutation in Slfn2 increases HSC proliferation. This additionally caused an increased amount of apoptotic stem and progenitor cells. Taken together, our findings demonstrate that dysregulation of Slfn2 results in a functional deficiency of primitive hematopoietic cells, which is particularly reflected by a drastically impaired ability to reconstitute the hematopoietic system following transplantation and an increase in HSC proliferation. This study thus identifies Slfn2 as a novel and critical regulator of adult HSC and HSC quiescence.

Management of the floating shoulder: Does the glenopolar angle influence outcomes? A systematic review.

INTRODUCTION: Currently there is no consensus on the optimal treatment of the "floating shoulder". We aim to perform a systematic review to determine outcomes in the management of this condition. MATERIALS AND METHODS: Studies related to the management of the "floating shoulder" were identified by a review of medline using platform Pubmed/Ovid, Scopus and Cochrane library data bases. Studies were included if they: (1) are published in the English language and (2) reported outcomes of at least 2 or more cases of floating shoulder injuries using at least one objective shoulder scoring system. Exclusion criteria were (1) non-human and biomechanical studies and (2) studies with a clear selection bias. Three treatment groups were identified. Group 1-non-operative, Group 2-fixation of clavicle only, and Group 3-fixation of clavicle and scapula neck. RESULTS: Thirteen studies gave a population of 244 subjects of which 104 had non-operative treatment, 98 had internal fixation of the clavicle only and 42 had fixation of both the clavicle and the scapula. There were no differences in the outcome scores among the 3 treatment arms as the patients with undisplaced or minimally displaced fractures had conservative treatment and those with displaced fractures were surgically stabilised. There was a positive correlation between the final glenopolar angle and the Constant score. CONCLUSIONS: The review was unable to show a difference in outcomes among the 3 treatment groups. Any treatment modality that restores the glenopolar angle is likely to result in a good outcome. LEVEL OF EVIDENCE: Therapeutic level IV.

A consensus on men's health status and policy in Asia: a Delphi survey.

OBJECTIVE: There is currently no documentation on the availability and implementation of policies related to men's health in Asia. This Delphi study aimed to achieve an Asian consensus on men's health policy based on the opinions and recommendations from men's health key opinion leaders. STUDY DESIGN: A two-phase Delphi online survey was used to gather information from men's health stakeholders across Asian countries. METHODS: All stakeholders were invited to participate in the survey through men's health conferences, personal contacts, recommendations from international men's health organizations and snowballing method. Stakeholders were asked about their concerns on 17 men's health key issues as well as their opinion on the availability and recommendations on men's health policies and programmes in their countries. RESULTS: There were a total of 128 stakeholders (policy makers, clinicians, researchers and consumers), from 28 Asian countries, who responded in the survey. Up to 85% of stakeholders were concerned about various men's health issues in Asia and in their respective country, particularly in smoking, ischaemic heart disease and high blood pressure. There is a lack of men's health policies and programmes in Asia (availability = 11.6-43.5%) and up to 92.9% of stakeholders recommended that these should be developed. CONCLUSIONS: These findings call for policy change and development, and more importantly a concerted effort to elevate men's health status in Asia.

The influence of enclosure design on diurnal activity and stereotypic behaviour in captive Malayan Sun bears (Helarctos malayanus).

The effect of enclosure design on diurnal activity and stereotypic behaviour was assessed in 17 adult Malayan Sun bears (Helarctos malayanus), kept either in barren indoor enclosures or relatively enriched outdoor enclosures. Locomotion was the most frequent activity observed in the indoor bears, followed by resting. In contrast, conspecifics housed outdoors spent most of the time resting. Eleven forms of stereotypic behaviours were recorded in the bears, with pacing being the most common. The frequency and repertoire of stereotypies were significantly higher in the indoor bears irrespective of enclosure size. Novel forms of locomotor (forward-reverse pacing) and oral (allo-sucking) stereotypies were recorded. Oral stereotypies were predominant in the bears housed indoors, while patrolling was confined to the outdoor bears. Enclosure complexity significantly influences activity budget and occurrence of stereotypic behaviours, highlighting the importance of appropriate enclosure design and enrichment for the welfare of captive bears.

Prediction and parametric analysis of thermal profiles within heated human skin using the boundary element method.

In this paper, an axisymmetric model of the human skin is developed to simulate the steady-state temperature distribution during contact with a hot solid. Simulations are carried out using the boundary element method. This study seeks to investigate the feasibility of using the boundary element method in the studies of burn. A sensitivity analysis is carried out to examine the effects of various parameters on the temperature distribution inside the skin during burn. Furthermore, a statistical analysis based on the Taguchi method is performed to determine the combination of factors that produce the desired outcome (least increase in temperature). In order to validate the accuracy of the numerical scheme, results obtained using the boundary element method are compared with the solutions obtained using the more established finite-element method.

Boundary element method with bioheat equation for skin burn injury.

Burns are second to vehicle crashes as the leading cause of non-intentional injury deaths in the United States. The survival of a burn patient actually depends on the seriousness of the burn. It is important to understand the physiology of burns for a successful treatment of a burn patient. This has prompted researchers to conduct investigations both numerically and experimentally to understand the thermal behaviour of the human skin when subjected to heat injury. In this study, a model of the human skin is developed where the steady state temperature during burns is simulated using the boundary element method (BEM). The BEM is used since it requires boundary only discretion and thus, reduces the requirement of high computer memory. The skin is modeled as three layered in axisymmetric coordinates. The three layers are the epidermis (uppermost), dermis (middle) and subcutaneous fat. Burning is applied via a heating disk which is assumed to be at constant temperature. The results predicted by the BEM model showed very good agreement with the results obtained using the finite element method (FEM). The good agreement despite using only linear elements as compared to quadratic elements in the FEM model shows the versatility of the BEM. A sensitivity analysis was conducted to investigate how changes in the values of certain skin variables such as the thermal conductivity and environmental conditions like the ambient convection coefficient affect the temperature distribution inside the skin. The Taguchi method was also applied to identify the combination of parameters which produces the largest increase in skin temperature during burns.

Estimation of fungal growth using the ergosterol assay: a rapid tool in assessing the microbiological status of grains and feeds.

AIM: To use ergosterol assay as a rapid tool to assess the extent of fungal contamination in grains and feeds. METHODS AND RESULTS: Ergosterol was extracted from moulds and quantified using a modified method based on Seitz et al. (1977). A good correlation coefficient of 0.9998 was obtained for ergosterol standards and a strong correlation (R(2) = 0 x 9645) was established between the ergosterol content and the growth of Aspergillus niger ATCC 24126. This shows that this assay can be used to estimate fungal growth. The ergosterol contents and amount of carbon dioxide produced in both Control and Myco CURB (brand) liquid-treated corns were measured over 36 days. Ergosterol contents of pelleted pig feeds were also determined. In both experiments, the levels of ergosterol in the control samples were significantly higher than those of the mould-inhibitor-treated samples. CONCLUSIONS: A strong positive correlation (Spearman, Rs = 0 x 7241) was observed between the ergosterol content and the degree of fungal growth. Hence, ergosterol assay can be used as a rapid tool to assess the microbiological status of grains and feeds. SIGNIFICANCE AND IMPACT OF THE STUDY: This study affirms that ergosterol assay is a rapid and accurate tool that can be used for the assessment of the feed quality.

Ultra-low dose combined spinal-epidural anesthesia with intrathecal bupivacaine 3.75 mg for cesarean delivery: a randomized controlled trial.

BACKGROUND: We wished to investigate the feasibility of an ultra low-dose combined spinal-epidural technique in providing surgical anesthesia for uncomplicated cesarean deliveries in a randomized, double-blind controlled trial. METHOD: Forty-four normotensive, non-obese patients were randomized to receive either intrathecal hyperbaric bupivacaine 3.75 mg (low dose group, n=22) or 9 mg (conventional group, n=22), in addition to intrathecal fentanyl 25 microg, morphine 100 microg, and epidural 1.5% lidocaine 3 mL. Sensorimotor anesthesia and hemodynamic data were assessed at 2.5-min intervals for the first 15 min. RESULTS: The maximal sensory block achieved in the low-dose group was significantly lower than that in the conventional group (median T3, [range T2-T6] vs. T2 [C2-T6], P<0.001) with a longer time taken to reach maximal sensory block. The low-dose group had less motor block, faster sensory regression to T10 dermatome and faster motor recovery to Bromage 0 (all P<0.001). The block failed to reach T6 bilaterally within 10 min in one patient in the low-dose group and two in the conventional group, with no significant difference in the need for epidural supplementation before or after delivery of the baby. The low-dose group experienced less hypotension (14% vs. 73%, P<0.001) with less ephedrine usage (0.68 vs. 17.5 mg, P<0.001). There was no difference in operating conditions and other side effects (shivering, pruritus). CONCLUSION: We conclude that this technique results in a significantly lower incidence of maternal hypotension and has a role in high-risk parturients in whom maintenance of stable hemodynamics is imperative.

Evaluation of surgical and anaesthesia response times for crash caesarean sections--an audit of a Singapore hospital.

INTRODUCTION: The Royal College of Obstetricians and Gynaecologists published the "Organisational Standards for Maternity Services" in 1995, in which they proposed that there be a maximum decision-to-delivery time of 30 minutes for urgent caesarean sections (CS). In 1997, our institution established a protocol for extremely urgent ("crash") CS to expedite delivery time and to conform to this standard. MATERIALS AND METHODS: The objective of this prospective audit was to determine the surgical and anaesthesia response times in our institution after the protocol had been implemented. The audit was conducted in KK Women's and Children's Hospital from February 2003 to January 2004, over a 12-month period. Upon activation of a "crash" CS, the attending anaesthetist was required to record the decision-to-anaesthesia time, decision-to-delivery time and the perinatal outcome. RESULTS: Ninety-eight cases of "crash" CS were identified from a total of 3629 elective and non-elective CS, with 80 cases having complete data. The mean decision-to-delivery interval was 7.7 min+/-3.0 (SD) with 100% of deliveries made within 17 minutes. The mean decision-to-anaesthesia time was 3.5 min+/-2.0 (SD) with all the patients anaesthetised within 10 minutes. The majority (88.8%) of the patients had general anaesthesia for "crash" CS while the rest had successful epidural block extension. There was no significant difference in the decision-to-delivery interval or mean cord blood pH with respect to the type of anaesthesia given. CONCLUSIONS: We achieved 100% deliveries within the proposed 30-minute decision-to-delivery time interval by implementing a protocol for "crash" CS. Both general anaesthesia and extension of existing epidural block are acceptable modes of anaesthesia and do not delay delivery of the fetus.

Migration of a foreign body in the maxillary sinus illustrating natural mucociliary action.

We present a case of a foreign body which migrated to the maxillary ostia by mucociliary action from its initial location on the floor of the maxillary sinus where it was traumatically introduced. This report illustrates that a powerful mechanism of mucociliary action can cause relatively heavy objects within the maxillary sinus to migrate naturally to the sinus ostia against gravitational force.

Analgesic efficacy of pre-operative etoricoxib for termination of pregnancy in an ambulatory centre.

INTRODUCTION: Etoricoxib is a second generation cyclooxygenase-2 inhibitor with a rapid-onset time and a long duration of action. It is ideal for providing pre-emptive analgesia for ambulatory surgeries. We hypothesised that pre-operative etoricoxib can decrease the use of fentanyl post-operatively, when compared with placebo in patients undergoing termination of pregnancy. We also compared their pain scores, time to discharge, side effects and satisfaction with analgesia post-operatively. METHODS: After approval by the hospital research ethics committee and receipt of informed written consent, we recruited 40 American Society of Anesthesiologists Physical Status Classification I and II patients scheduled for elective first trimester termination of pregnancy. Patients were randomly allocated to receive either oral etoricoxib 120 mg (Group E, n=20) or placebo tablet (Group P, n=20) pre-operatively. A blinded observer evaluated the post-operative pain scores, need for supplementary analgesia, side effects and satisfaction scores. Sample size was calculated (power of 0.8 and alpha=0.05) to detect a 20 percent difference in fentanyl usage. Amount of fentanyl used, pain scores and satisfaction scores were analysed using non-parametric tests. The incidence of side effects was analysed using chi-squared test. RESULTS: Etoricoxib 120 mg significantly decreased the amount of fentanyl required after termination of pregnancy compared to placebo (0 microg/patient, interquartile range [IQR] 0-25 versus 50 microg/patient, IQR 0-50, p-value is less than 0.05). Patients who received etoricoxib 120 mg also had significantly lower pain scores than the placebo group at time of discharge (8 +/- 11 versus 1 +/- 3, p-value is less than 0.05) and at six hours post operation (8 +/- 12 versus 0 +/- 0, p-value is less than 0.01). There was no difference in their side effects, and time to discharge and overall satisfaction were similar in both groups. CONCLUSION: Pre-operative administration of oral etoricoxib 120 mg decreased the use of fentanyl and pain scores after minor gynaecological surgery without significant side effects.

Facial palsy from temporal bone lesions.

INTRODUCTION: Facial nerve palsy results in the loss of facial expression and is most commonly caused by a benign self-limiting inflammatory condition, known as Bell's palsy. However, there are other conditions which may result in injury of the seventh cranial nerve and the radiologist should be familiar with their imaging appearances. MATERIALS AND METHODS: The relevant anatomy of the facial nerve and pathology which may affect the intratemporal portion of the nerve is described. The role of imaging and choice of imaging modality is also reviewed. RESULTS: High-resolution computer tomography(HRCT) images of the temporal bone and magnetic resonance(MR) images of the facial nerve from 11 patients who presented with facial nerve palsy were used to illustrate how intratemporal facial nerve injury of other aetiologies can mimic Bell's palsy. The typical imaging appearance of Bell's palsy was also presented. CONCLUSIONS: Most patients with suspected Bell's palsy do not require radiologic imaging. However, when symptoms progress, persist or when there is multiple cranial nerve involvement, recurrent symptoms or subacute onset of facial nerve palsy, causes other than Bell's palsy should be considered.

Migration of a foreign body in the maxillary sinus illustrating natural mucociliary action.

We present a case of a foreign body which migrated to the maxillary ostia by mucociliary action from its initial location on the floor of the maxillary sinus where it was traumatically introduced. This report illustrates that a powerful mechanism of mucociliary action can cause relatively heavy objects within the maxillary sinus to migrate naturally to the sinus ostia against gravitational force.

Audit of diagnostic and interventional craniocervical catheter angiographic procedures at the Singapore General Hospital.

INTRODUCTION: Catheter angiography is an established imaging modality of evaluating cerebral and head and neck vascular diseases. It is, however, an invasive procedure with a small risk of complications. The aim of our study was to evaluate the prevalence of peri-procedural complications in a local hospital setting. MATERIALS AND METHODS: A total of 88 patients underwent diagnostic and interventional craniocervical procedures over 6 months in our department. The casenotes of 83 patients were retrospectively reviewed for complications arising from a total of 99 procedures carried out. RESULTS: A new focal neurological deficit developed in 3 different patients after a procedure, giving a prevalence of 3.0%. All these occurred in diagnostic procedures and were permanent deficits with correlative computed tomography (CT) or magnetic resonance (MR) imaging findings of acute cerebral infarction. All these occurred in high-risk patients who had severe underlying cerebrocarotid vascular compromise. There was 1 case of contrast medium-induced nephropathy (1.0%), occurring in a patient with pre-existing renal impairment. Local complications included 1 case of iatrogenic external iliac artery dissection (1.0%) and 5 cases (5.1%) of small and uncomplicated puncture site groin haematomas. CONCLUSION: The most significant complication associated with a craniocervical angiographic procedure was the development of post-procedural stroke in patients with significant preexisting cerebrocarotid vascular compromise. In the absence of this risk factor, craniocervical catheter angiography is a relatively safe procedure.

Monophasic, solitary tumefactive demyelinating lesion: neuroimaging features and neuropathological diagnosis.

The characteristic clinicoradiological findings of multiple sclerosis and acute disseminated encephalomyelitis (ADEM), demonstrating a recurrent progressive course in the former and monophasicity in the latter associated with multiple discrete white matter lesions with variable enhancement on MRI, are not a diagnostic challenge. On the other hand, the less typical radiological presentation of a solitary tumefactive demyelinating lesion mimics a neoplasm, and often necessitates a biopsy. Nonetheless, histopathological examination is an imperfect gold standard and the recognition of certain imaging features may facilitate the correct diagnosis.

[Comparison of preemptive analgesia efficacy between etoricoxib and rofecoxib in ambulatory gynecological surgery].

OBJECTIVE: To compare the preemptive analgesia efficacy between two cycloxygenase-2 inhibitors, rofecoxib and etoricoxib in the ambulatory uterine evacuation patients. METHODS: In this randomized, double-blinded, placebo-controlled trial 60 patients were randomly divided into three groups and received a single dose of placebo, rofecoxib 50 mg, or etoricoxib 120 mg, respectively, before operation. Patient's visual analogue score (VAS) was rated postoperatively at 15 min, 30 min, 60 min, time-to-discharge, 6 h and 24 h. Fentanyl (in post-anesthesia care unit) and paracetamol (at home) were supplementary analgesics and the dosage was also recorded. Patient's satisfaction score was rated at 24 h postoperatively. RESULTS: Etoricoxib 120 mg and rofecoxib 50 mg were significantly superior to placebo at 6 h postoperatively (P < 0.05) while there was no significant differences of VAS at other time points. The amounts of Fentanyl used in post-anesthesia care unit were similar in three groups, but paracetamol taken at home was much less in rofecoxib group and etoricoxib group than in placebo group (P < 0.01). Compared to rofecoxib, etoricoxib provided better pain relief after discharge (P < 0.05). The overall pain management satisfaction score was significantly higher in etoricoxib group (96 +/- 7) than in other groups (P < 0.01). CONCLUSION: Preemptive rofecoxib 50 mg and etoricoxib 120 mg may significantly decrease VAS at 6 h postoperatively, and reduce the usage of analgesics in ambulatory uterine evacuation patients. Etoricoxib 120 mg offeres better pain relief at home compared with rofecoxib 50 mg.

Pancreatitis leading to retroperitoneal fibrosis and ureteric obstruction.

Two patients who had acute pancreatitis subsequently developed characteristic appearance on urography of smooth extrinsic narrowing and medial deviation of the right ureter suggestive of retroperitoneal fibrosis (RPF) resulting in ureteric obstruction. Both these patients had clinical, biochemical and sonographic evidence of acute pancreatitis. CT scan of the abdomen performed on the second patient also documented acute pancreatitis. Intravenous urograms were consistent with ureteric obstruction due to retroperitoneal fibrosis. Both cases were treated conservatively. They were well after an average of 20 months. These 2 cases illustrate the uncommon association between pancreatitis and RPF.