Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of ...BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison to the inhibitors of the neuronal death signaling cascade; these, in fact, can attenuate the infarct volume measured at 24 h post-ischemia when administered at 6 h in our same stroke model.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•HEPA-ClO2 with contact-killing and release-killing properties against microbes.•HEPA-ClO2 with effective in filtering and killing viruses, bacteria, and spores.•HEPA-ClO2 is safe ...according to in-vitro and in-vivo studies.•HEPA-ClO2 is more efficient than unmodified HEPA in field trial and CFD studies.
Pathogenic microbes in the air are the leading cause of respiratory diseases and illnesses, and respiratory viruses are responsible for some of the world’s most devastating epidemics and pandemics. Therefore, their capture, removal, and disinfection are essential in preventing the spread of diseases. A multilevel antimicrobial HEPA-ClO2 prepared by coating micro-encapsulated chlorine dioxide on high-efficiency particulate air (HEPA-H13) filter, displays broad-spectrum virucidal and bactericidal, as well as sporicidal activities through the combined “contact-killing” and “release-killing” properties. In-vitro cytotoxicity (i.e., human A549 cells) and in-vivo inhalation toxicity tests (i.e., Kunming mice) indicate HEPA-ClO2 has low inhalation toxicity and is safe. Furthermore, it has superb performance against a panel of infectious respiratory viruses (e.g., influenza viruses, EV-71) and bacteria (e.g., L. pneumophila, K. pneumonia) and drug-resistant organisms (e.g., MRSA, MRPA), attaining log 2 reduction (99%) within a minute. However, spores required 30 min to reach 99% inactivation. A 260-day field trial study at a palliative care facility demonstrated that air purifiers could significantly decrease airborne particulates and microbes (bacteria and mold/fungi) and confirmed the long-term efficacy of the HEPA-ClO2 filters and their superiority over uncoated HEPA-H13 against microbes. The experimental results from the wardroom were validated by a computational fluid dynamics (CFD) simulation.
Isoflurane protects the blood-brain barrier (BBB) against cerebral extravasation of Evans blue dye (EBD), a commonly used serum protein tracer, in animals subjected to BBB disruption. As such, it has ...been implicated as a therapeutic agent that can prevent brain edema and damage caused by a number of brain insults, including focal ischemia and subarachnoid hemorrhage. Recently, it has been shown that isoflurane inhibits the cerebral extravasation of EBD following ischemic stroke chiefly by inducing hypothermia, raising the intriguing possibility that isoflurane protected against other causes of BBB disruption also through hypothermia. To test this hypothesis, we subjected mice and rats to inhalation of 20-30% carbogen, an inducer of BBB disruption, in the presence or absence of isoflurane while measuring their rectal temperature. In mice, carbogen inhalation on its own decreased rectal temperature from 36.4 ± 0.4 to 26.2 ± 0.6°C over a period of 60 minutes, and under this condition, isoflurane had no additional effect on body temperature. Nevertheless, isoflurane protected against carbogen-induced cerebral extravasation of EBD. In addition, when the body temperature was maintained in the normothermic range using an automated heating pad, isoflurane remained protective against cerebral extravasation of EBD. In rats, isoflurane also protected against cerebral extravasation of EBD, while having no effect on plasma pH, electrolyte concentrations, or osmolarity. In conclusion, isoflurane protected against BBB disruption caused by carbogen inhalation in mice and rats, but unlike isoflurane-mediated protection against ischemic BBB disruption, the effect could not be explained by anesthesia-induced hypothermia.
Highly reactive rhodium(III) porphyrin hydroxides were formed from the ligand substitution of rhodium porphyrin halides in benzene and were rapidly reduced to rhodium(II) porphyrins and hydrogen ...peroxide. Thus hydroxide acted as the reducing agent. Oxidative addition of rhodium(II) porphyrin with hydrogen peroxide proceeded rapidly at room temperature to give back rhodium(III) porphyrin hydroxides. Rhodium(II) porphyrins and H2O2 therefore were thermally reversible with rhodium porphyrin hydroxides.
Er-xian Decoction (EXD), containing Herba epimedii Maxim (HEP) and Curculigo orchioides Gaertn (XM) as principal drugs, is a traditional Chinese medicine (TCM) formula prescribed for the treatment of ...postmenopausal osteoporosis. In the present study, the in vivo anti-osteoporosis effects of EXD, HEP and XM on four-month-old ovariectomized (OVX) Sprague-Dawley rats were investigated. Micro-computed tomography analysis showed that EXD could significantly improve the micro-architectural parameters (BMD, BV/TV, Tb.N, Tb.Th, and Tb.Sp) of trabecular bone in the distal femur and proximal tibia in OVX rats (p < 0.05). The biomechanical parameters of the distal femur in rats treated with EXD were also improved significantly (p < 0.05 vs. OVX group). The in vivo efficacy of EXD was found to be superior to HEP or XM alone in improving the bone properties of OVX rats. Treatment of rat osteoblastic-like UMR-106 cells with EXD, HEP, and XM significantly promoted the cell proliferation rate (p < 0.05) with the most promising effects observed in cells treated with EXD (p < 0.001). The proliferative effect in UMR-106 cells induced by EXD, HEP, and XM were abolished in the presence of the estrogen antagonist, ICI182780, suggesting that their effects were mediated by estrogen receptor (ER). Additionally, EXD could activate ER-α and ER-β mediated estrogen-response element (ERE)-dependent luciferase activity as well as phosphorylate ER-α at serine 118 in UMR-106 cells. Taken together, EXD offered better osteoprotective effects than its single principal herb, and the beneficial effects of EXD in preventing bone deteriorations are, at least partially, through the ER signaling pathway.
Rapid whole-exome sequencing (rWES) offers the potential for early diagnosis-predicated precision medicine. Previous evidence focused predominantly on infants from the intensive care unit (ICU). This ...study sought to examine the diagnostic and clinical utility, and the economic impact on clinical management of rWES in patients beyond infancy and ICU setting.
rWES was performed on a prospective cohort of patients with suspected monogenic disorder referred from territory-wide paediatric ICUs and non-ICUs in Hong Kong urging for rapid genetic diagnosis. All eligible families were invited. We aimed to achieve a rapid turnaround time (TAT) of 14 days. Clinical utility and costs associated with clinical management were assessed in diagnosed cases. Actual quantitative changes in healthcare utilisation were compared with a counterfactual diagnostic trajectory and/or with matched historical control whenever possible.
rWES were offered to 102 families and 32/102 (31%) patients received a molecular diagnosis, with a median TAT of 11 days. Clinical management changed in 28 of 32 diagnosed patients (88%), including but not limited to modifications in treatment, avoidance of surgeries, and informing decisions on redirection of care. Cost analysis was performed in eight patients. rWES was estimated to reduce hospital length of stay by 566 days and decrease healthcare costs by HKD$8,044,250 (GBP£796,460) for these eight patients. The net cost-savings after inclusion of rWES costs were estimated to be HKD$5,325,187 (GBP£527,246).
This study replicates the diagnostic capacity and rapid TAT of rWES in predominantly Chinese patients, and demonstrates diagnosis-predicated precision medicine and net healthcare savings. Findings were corroborated by evidence from multinational cohorts, combined as part of a meta-analysis. rWES merits consideration as a first-tier diagnostic tool for patients with urgent needs in the clinical setting.
Health and Medical Research Fund, HKU Seed Fund for Basic Research, The Society for the Relief of Disabled Children, and Edward and Yolanda Wong Fund.
The year 2022 marks the 30th anniversary of heart transplant service in Hong Kong (HK). In this study, we describe prevailing trends and outcomes of advanced heart failure (AHF), including heart ...transplantations (HTx), in HK over the past 30 years.
Trends in heart failure prevalence in HK from 1993 to 2021 were analyzed based on data from the Hospital Authority Clinical Data and Reporting System. All AHF patients referred for HTx consideration between 1992 and 2021 were reviewed. The bridge-to-transplant (BTT) utilization of short-term mechanical circulatory support (ST-MCS) devices, including venoarterial extracorporeal membrane oxygenation (VA-ECMO) and durable left ventricular assist devices (LVADs), from 2010 to 2021 was reviewed.
Overall, 237 heart transplants were performed in HK, with 10-year posttransplant and median survival of 68.1% and 18.7 years, respectively. An increase in AHF clinic referrals was correlated with increasing heart failure prevalence (R
=0.635, P<0.001). In total, 146 referrals were made for ST-MCS, and an observed increase in ST-MCS referrals was correlated with increasing VA-ECMO utilization (R
=0.849, P<0.001). Among 62 patients accepted for AHF therapy, those with durable LVAD implementation had better 1-year survival (71.5%) than those receiving an extracorporeal CentriMag (Levitronix) device as BTT (40%, P=0.008). In total, 143 LVADs were implanted, with 130 as BTT or bridge-to-candidacy (BTC) methods. The survival rate among the 130 BTT/BTC LVAD patients resembled that of HTx recipients (73.8% vs. 69.8% at 9 years, P=0.296).
The burden of AHF management has increased and gained complexity over the past 30 years in Hong Kong.
AIM: To evaluate the outcome after surgery for unilateral superior oblique(SO) palsy in Chinese.METHODS: The medical records of 39 patients that underwent surgery for unilateral SO palsy between ...January 2003 and December 2012 at Caritas Medical Centre, Hong Kong, were retrospectively reviewed. All surgeries were performed by a single surgeon. Pre-operative assessments for vertical deviation, cyclo-deviation, and Knapp’s classification were obtained to determine the nature and degree of surgical correction.Vertical deviation was measured at 1wk; 1, 6mo and on last follow-up day post-operatively. Cyclo-deviation was measured on last follow-up day post-operatively.RESULTS: During the 10 y period, 39 subjects were recruited. The most common etiology was congenital(94.9%). Knapp’s Type III(66.7%) and Type I(12.8%)classifications were the most common subtypes. To treat SO palsy, the most common surgical procedures were:isolated inferior oblique(IO) anteriorization(41.0%),isolated IO myectomy(10.3%), and isolated IO recession(10.3%). At 3.5 ±2.1y post-operatively, the vertical deviation was significantly reduced(15.1 ±6.2 PD versus0.5±1.4 PD, P <0.0001) without significant improvement in cyclo-deviation(P =0.5). Initial vertical deviation was correlated with cyclo-torsion(r =0.4, P =0.007). Those with over-correction had greater initial vertical deviation(19.4±7.2 PD versus 13.2±4.3 PD, P =0.003). After a single operation, 84.6% of subjects achieved a vertical deviation within ±3 PD.· CONCLUSION: The majority of subjects achieved corrected vertical deviation after a single surgery although there was no improvement in cyclo-deviation.Those with over-correction of primary position deviation had greater preoperative vertical deviation and it may be related to simultaneous multiple muscle surgery.
An interesting rhodium‐catalyzed asymmetric aqueous Pauson–Khand‐type reaction was developed. A chiral atropisomeric dipyridyldiphosphane ligand was found to be highly effective in this system. This ...operationally simple protocol allows both catalyst and reactants to be handled under air without precautions. Various enynes were transformed to the corresponding bicyclic cyclopentenones in good yield and enantiomeric excess (up to 95 % ee). A study of the electronic effects of the enyne substrates revealed a correlation between the electronic properties of the substrates and the ee value obtained in the product of the Pauson–Khand‐type reaction. A linear free‐energy relationship was observed from a Hammett study.
Making rings in water: Asymmetric Pauson–Khand‐type cyclizations were accomplished with a chiral rhodium–P‐Phos complex at 100 °C in aqueous conditions (see scheme; cod=cycloocta‐1,5‐diene, Ts=toluene‐4‐sulfonyl). An interesting electronic effect was observed between the electronic properties of the substrates and the enantiomeric excess of the products in a Hammett study.
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