Window For Effective Treatment Research Articles

Plasmonic nanobipyramids with photo-enhanced catalytic activity under near-infrared II window for effective treatment of breast cancer

Nanozyme-based catalytic therapy is an effective method for cancer treatment, but insufficient catalytic activity presents a challenge in achieving optimal therapeutic outcomes. External light can provide an innovative approach to modulate nanozyme catalytic activity. Herein, we report on plasmonic gold nanobipyramid@cuprous oxide (Au NBP@Cu2O) nanozyme for the effective phototherapy of breast cancer. In the tumor microenvironment, Cu+-mediated Fenton-like reaction catalyzes the generation of toxic hydroxyl radicals (•OH) from endogenous hydrogen peroxide to induce apoptosis. Additionally, the Au NBP@Cu2O nanostructure improves the absorption performance of Au NBPs in the near-infrared II region through near-field enhancement of equipartite exciters and achieves a high photothermal conversion efficiency value of 58%. Remarkably, the Au NBP@Cu2O nanoheterostructure can capture hot electrons induced by equipartition excitations and promote electron-hole separation under 1064 nm laser irradiation, facilitating the production of more reactive oxygen species (ROS). The mechanism behind this enhanced catalytic activity was unraveled using femtosecond transient absorption spectroscopy. Both in vitro and in vivo investigations have demonstrated the efficacious tumor therapeutic potential of Au NBP@Cu2O nanozyme, particularly under 1064 nm laser irradiation. Furthermore, the proposed therapeutic approach has been proved to effectively block tumor metastasis, providing a promising strategy for the development of multifunctional nanotherapeutics to tackle metastatic tumors. Statement of significanceA highly effective plasmonic nanozyme has been developed to improve catalytic therapy for breast cancer. When exposed to 1064 nm laser irradiation, Au NBP@Cu2O nanozyme can promote the separation of hot electrons and holes thereby facilitating the production of reactive oxygen species. Hot electrons transfer behavior is unveiled by femtosecond transient absorption spectroscopy technique. This enhanced catalytic activity, along with the intrinsic photothermal effect, effectively kills tumor cells.

A study on skin tumor classification based on dense convolutional networks with fused metadata.

Skin cancer is the most common cause of death in humans. Statistics show that competent dermatologists have a diagnostic accuracy rate of less than 80%, while inexperienced dermatologists have a diagnostic accuracy rate of less than 60%. The higher rate of misdiagnosis will cause many patients to miss the most effective treatment window, risking the patients' life safety. However, the majority of the current study of neural network-based skin cancer diagnosis remains at the image level without patient clinical data. A deep convolutional network incorporating clinical patient metadata of skin cancer is presented to realize the classification model of skin cancer in order to further increase the accuracy of skin cancer diagnosis. There are three basic steps in the approach. First, the high-level features (edge features, color features, texture features, form features, etc.). Implied by the image were retrieved using the pre-trained DenseNet-169 model on the ImageNet dataset. Second, the MetaNet module is introduced, which uses metadata to control a certain portion of each feature channel in the DenseNet-169 network in order to produce weighted features. The MetaBlock module was added at the same time to improve the features retrieved from photos using metadata, choosing the most pertinent characteristics in accordance with the metadata data. The features of the MetaNet and MetaBlock modules were finally combined to create the MD-Net module, which was then used as input into the classifier to get the classification results for skin cancers. On the PAD-UFES-20 and ISIC 2019 datasets, the suggested methodology was assessed. The DenseNet-169 network model combined with this module, according to experimental data, obtains 81.4% in the balancing accuracy index, and its diagnostic accuracy is up between 8% and 15.6% compared to earlier efforts. Additionally, it solves the problem of actinic keratosis and poorly classified skin fibromas.

Prize‐winning abstracts from BSACI/WAO 2022 meeting

Prize‐winning abstracts from <scp>BSACI</scp>/<scp>WAO</scp> 2022 meeting

Clinical examination and patients' history are not suitable for neonatal hip screening.

Purpose:To assess the percentage of missed developmental dysplasia of the hip, which escape the German criteria for newborn hip high-risk screening, we analyzed our data gained from the general neonatal sonographic hip screening performed at our department. The aim of the study was to determine the number of potentially belatedly treated developmental dysplasia of the hip.Methods:The data from 1145 standardized newborn hip ultrasound examinations according to the Graf technique were analyzed retrospectively comparing findings for general neonatal sonographic hip screening and high-risk screening subgroups.Results:We diagnosed developmental dysplasia of the hip in 18 of the 1145 newborns via ultrasound. A total of 10 out of 18 developmental dysplasia of the hip would have been missed by high-risk screening, which corresponds to a proportion of 55.6% false-negative results. The sensitivity of high-risk screening was only 44.4% and specificity, 78.3%. The positive predictive value was 3.2%. Family history as a screening criterion yielded false-negative results in 77.8% and false-positive results in 16.8%. In all, 83.3% of the children who were born with developmental dysplasia of the hip but not from breech position as a risk factor were false negative. The clinical examination was false negative in 88.9% and false positive in 0.6%.Conclusion:High-risk screening detected less than every second developmental dysplasia of the hip, rendering the first month as the most effective treatment window unavailable for inapparent dysplastic hips, potentially resulting in the need for more invasive treatment. Due to the high sensitivity of ultrasound in the detection of developmental dysplasia of the hip, we recommend to replace the current German high-risk screening guidelines with a general newborn screening for all neonates using Graf ultrasound in the first week of life.Level of evidence:Level II.

Harnessing the Potential of miRNAs in Malaria Diagnostic and Prevention.

Despite encouraging progress over the past decade, malaria remains a major global health challenge. Its severe form accounts for the majority of malaria-related deaths, and early diagnosis is key for a positive outcome. However, this is hindered by the non-specific symptoms caused by malaria, which often overlap with those of other viral, bacterial and parasitic infections. In addition, current tools are unable to detect the nature and degree of vital organ dysfunction associated with severe malaria, as complications develop silently until the effective treatment window is closed. It is therefore crucial to identify cheap and reliable early biomarkers of this wide-spectrum disease. microRNAs (miRNAs), a class of small non-coding RNAs, are rapidly released into the blood circulation upon physiological changes, including infection and organ damage. The present review details our current knowledge of miRNAs as biomarkers of specific organ dysfunction in patients with malaria, and both promising candidates identified by pre-clinical models and important knowledge gaps are highlighted for future evaluation in humans. miRNAs associated with infected vectors are also described, with a view to expandind this rapidly growing field of research to malaria transmission and surveillance.

Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia-Induced Neurodegeneration in the Brain and Retina.

Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).

Prevalence of delayed diagnosis of acute ischemic stroke in an acute care hospital: A single-center cross-sectional study in Japan.

BackgroundsGiven the short therapeutic window for evidence‐based therapies such as thrombolysis and endovascular treatment, it is important to immediately diagnose ischemic stroke. We investigated the prevalence of missed ischemic stroke diagnoses at initial contact and the proportion of potentially treatable patients without a delayed diagnosis.MethodsA cross‐sectional study was conducted. A total of 408 consecutive patients hospitalized due to acute ischemic stroke were included. The primary outcome was a delayed diagnosis of ischemic stroke at initial contact. A diagnosis of stroke was judged to be delayed unless physicians made a diagnosis and initiated treatment for ischemic stroke during the initial contact. The secondary outcome was ischemic stroke with a missed therapeutic window for effective treatment due to delayed diagnosis.ResultsThe median patient age was 78 years old, and the median time from onset to presentation was nine hours. A diagnosis of stroke was deemed delayed in 49 (12.0%) patients. In the multivariable analysis, presentation 48 hours or more after stroke onset (OR 2.45) and the improvement of neurological symptoms prior to presentation (OR 3.11) were independently associated with delayed diagnosis of ischemic stroke. Opportunities for effective treatment were missed in 18 (36.7%) of the 49 delayed diagnosis cases, although no patients missed opportunities for thrombectomy due to delayed diagnosis.ConclusionsEven in the modern era, one out of every eight ischemic stroke cases was missed at the initial visit, and one‐third of missed stroke cases might be candidates for effective treatment without diagnostic delay.

Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B1

Mycotoxins, such as aflatoxin B1 (AFB1), pose a serious threat as biological weapons due to their high toxicity, environmental stability, easy accessibility and lack of effective therapeutics. This study investigated if blood purification therapy with CytoSorb (CS) porous polymer beads could improve survival after a lethal aflatoxin dose (LD90). The effective treatment window and potential therapeutic mechanisms were also investigated. Sprague Dawley rats received a lethal dose of AFB1 (0.5–1.0 mg/kg) intravenously and hemoperfusion with a CS or Control device was initiated immediately, or after 30, 90, or 240-minute delays and conducted for 4 hours. The CS device removes AFB1 from circulation and significantly improves survival when initiated within 90 minutes of toxin administration. Treated subjects exhibited improved liver morphology and health scores. Changes in the levels of cytokines, leukocytes and platelets indicate a moderately-severe inflammatory response to acute toxin exposure. Quantitative proteomic analysis showed significant changes in the level of a broad spectrum of plasma proteins including serine protease/endopeptidase inhibitors, coagulation factors, complement proteins, carbonic anhydrases, and redox enzymes that ostensibly contribute to the therapeutic effect. Together, these results suggest that hemoadsorption with CS could be a viable countermeasure against acute mycotoxin exposure.

Enaminone Modulators of Extrasynaptic α4β3δ γ-Aminobutyric AcidA Receptors Reverse Electrographic Status Epilepticus in the Rat After Acute Organophosphorus Poisoning.

Seizures induced by organophosphorus nerve agent exposure become refractory to treatment with benzodiazepines because these drugs engage synaptic γ-aminobutyric acid-A receptors (GABAARs) that rapidly internalize during status epilepticus (SE). Extrasynaptic GABAARs, such as those containing α4β3δ subunits, are a putative pharmacological target to comprehensively manage nerve agent-induced seizures since they do not internalize during SE and are continuously available for activation. Neurosteroids related to allopregnanolone have been tested as a possible replacement for benzodiazepines because they target both synaptic and extrasynaptic GABAARs receptors. A longer effective treatment window, extended treatment efficacy, and enhanced neuroprotection represent significant advantages of neurosteroids over benzodiazepines. However, neurosteroid use is limited by poor physicochemical properties arising from the intrinsic requirement of the pregnane steroid core structure for efficacy rendering drug formulation problematic. We tested a non-steroidal enaminone GABAAR modulator that interacts with both synaptic and extrasynaptic GABAARs on a binding site distinct from neurosteroids or benzodiazepines for efficacy to control electrographic SE induced by diisopropyl fluorophosphate or soman intoxication in rats. Animals were treated with standard antidotes, and experimental therapeutic treatment was given following 1 h (diisopropyl fluorophosphate model) or 20 min (soman model) after SE onset. We found that the enaminone 2-261 had an extended duration of seizure termination (>10 h) in the diisopropyl fluorophosphate intoxication model in the presence or absence of midazolam (MDZ). 2-261 also moderately potentiated MDZ in the soman-induced seizure model but had limited efficacy as a stand-alone anticonvulsant treatment due to slow onset of action. 2-261 significantly reduced neuronal death in brain areas associated with either diisopropyl fluorophosphate- or soman-induced SE. 2-261 represents an alternate chemical template from neurosteroids for enhancing extrasynaptic α4β3δ GABAAR activity to reverse SE from organophosphorous intoxication.

Efficacy of anti-inflammatory, antibiotic and pleiotropic agents in reversing nitrogen mustard-induced injury in ex vivo cultured rabbit cornea

Vesicating agent, Sulfur mustard (SM), causes devastating eye injury; however, there are no effective antidotes available. Using nitrogen mustard (NM), a bi-functional analog of SM, we have earlier reported that NM-induced corneal injury in ex vivo rabbit cornea organ culture model parallels corneal injury reported with SM. Using this model, we have demonstrated the therapeutic efficacy of dexamethasone (DEX), doxycycline (DOX) and silibinin (SB) in reversing NM (2h exposure)-induced corneal injuries when added immediately after washing NM. In the present study, we further examined the efficacy of similar/higher doses of these agents when added immediately, 2, or 4h after washing NM following its 2h exposure. All three treatment agents caused a reversal in established NM-induced injury biomarkers when added immediately or 2h after washing NM following its 2h exposure; however, when treatments were carried out 4h after washing NM, there was no significant effect. Together, our results further show the beneficial effect of these agents in reversing NM-induced corneal injury and indicate the time window for effective treatment. This could be useful towards future development of targeted therapeutics against vesicant-induced ocular injury.

Candidate proteins from predegenerated nerve exert time-specific protection of retinal ganglion cells in glaucoma

Glaucoma is thought to be the main cause of severe visual impairment or permanent loss of vision. Current therapeutic strategies are not sufficient to protect against glaucoma. Thus, new therapies and potential novel therapeutic targets must be developed to achieve progress in the treatment of this insidious disease. This study was undertaken to verify whether the time of administration of an extract from predegenerated rat sciatic nerves as well as exposure time of this extract onto retinal ganglion cells (RGCs) influences the survival of RGCs in a rat glaucoma model. We have demonstrated that extract obtained from the predegenerated sciatic nerves protects RGCs in a rat glaucoma model. The neuroprotective effect depends mostly on the time of administration of the extract and less clearly on the time of exposure to the extract and is associated with stimulation of endogenous BDNF expression both in RGCs and glial cells. The 14th day following glaucoma induction represents a therapeutic window for effective treatment in a glaucoma model. Mass Spectrometry analysis demonstrated that metallothionein 2 (MT2) may be a key molecule responsible for neuroprotective effects on RGC survival.

Estimation of Time Period for Effective Human Inhalational Anthrax Treatment Including Antitoxin Therapy.

Introduction:Infrequent natural human inhalational anthrax cases coupled with high bioterrorism risk have brought about use of animal models to serve as the basis for approval of novel treatments. For inhalational anthrax, protective antigen (PA) drives much of the mortality, and raxibacumab, an anti-PA monoclonal antibody, has been approved for therapeutic use using the Animal Rule. Given the paucity of human inhalational anthrax clinical data including PA kinetics, the post-exposure period for effective treatment of human disease remains unknown. The objective of this investigation was to extrapolate animal PA kinetics to a conceptual human model to estimate the post-exposure period for effective treatment of human inhalational anthrax.Methods:Human PA kinetic parameters were extrapolated from reported rabbit and monkey data. PA profiles were simulated with and without antibiotic induced PA clearance to represent antibiotic-sensitive and -resistant infections, respectively. Antitoxin levels equimolar to or greater than concurrent PA levels were considered protective.Results:For antibiotic sensitive infections, treatment with antibiotics alone ≤4 days after spore exposure prevents toxemia. Administration of raxibacumab together with antibiotics protects ≥ 80% of subjects for 3 additional days (7 days post exposure). In the setting of antibiotic resistance, raxibacumab would be protective for at least 6 days post exposure.Conclusions:Although the animal model of disease does not reflect the potential impact of supportive care (e.g. fluid resuscitation received by critically ill patients) on PA kinetics and raxibacumab PK, the simulations suggest that administration of antitoxin in combination with antibiotics should provide a longer postexposure window for effective treatment than for antibiotics alone. In addition, raxibacumab administration soon after exposure to an antibiotic resistant strain should provide effective treatment.

The impact of skin decontamination on the time window for effective treatment of percutaneous VX exposure

The main goal of the present study was to obtain insight into depot formation and penetration following percutaneous VX poisoning, in order to identify an appropriate decontamination window that can enhance or support medical countermeasures.The study was executed in two phases, using the hairless guinea pig as an animal model. In the first phase the effect of various decontamination regimens on levels of free VX in skin and plasma were studied as well as on blood cholinesterase levels. Animals were exposed to 0.5 mg/kg VX and were not decontaminated (control), decontaminated with RSDL once at 15 or 90 min after exposure or three times at 15, 25 and 35 (10-min interval) or 15, 45 and 75 min after exposure (30-min interval).There was no significant effect of any of the decontamination regimens on the 6-h survival rate of the animals. However, all animals that had been decontaminated 15 min after exposure, showed a survival rate of more than 90%, compared to 50–60% in animals that were not decontaminated or decontaminated at 90 min after exposure.In the second phase of the study, hairless guinea pigs were exposed to 1 mg/kg VX on the shoulder, followed either by decontamination with RSDL (10 min interval), conventional treatment on indication of clinical signs or a combination thereof. It appeared that a thorough, repeated decontamination alone could not save the majority of the animals. A 100% survival rate was observed in the group that received a combination of decontamination and treatment.In conclusion, the effects of VX exposure could be influenced by various RSDL decontamination regimens. The results in freely moving animals showed that skin decontamination, although not fully effective in removing all VX from the skin and skin depot is crucial to support pharmacological intervention.

A study on the natural history of scanning behaviour in patients with visual field defects after stroke

BackgroundA visual field defect (VFD) is a common consequence of stroke with a detrimental effect upon the survivors’ functional ability and quality of life. The identification of effective treatments for VFD is a key priority relating to life post-stroke. Understanding the natural evolution of scanning compensation over time may have important ramifications for the development of efficacious therapies.The study aims to unravel the natural history of visual scanning behaviour in patients with VFD. The assessment of scanning patterns in the acute to chronic stages of stroke will reveal who does and does not learn to compensate for vision loss.Methods/DesignEye-tracking glasses are used to delineate eye movements in a cohort of 100 stroke patients immediately after stroke, and additionally at 6 and 12 months post-stroke. The longitudinal study will assess eye movements in static (sitting) and dynamic (walking) conditions.The primary outcome constitutes the change of lateral eye movements from the acute to chronic stages of stroke. Secondary outcomes include changes of lateral eye movements over time as a function of subgroup characteristics, such as side of VFD, stroke location, stroke severity and cognitive functioning.DiscussionThe longitudinal comparison of patients who do and do not learn compensatory scanning techniques may reveal important prognostic markers of natural recovery. Importantly, it may also help to determine the most effective treatment window for visual rehabilitation.

Early, But Not Late Onset Estrogen Replacement Therapy Prevents Oxidative Stress and Metabolic Alterations Caused by Ovariectomy

The usefulness of estrogen replacement therapy (ERT) in preventing oxidative stress associated with menopause is controversial. We aimed to study if there is a critical time window for effective treatment of the effects of ovariectomy with estrogens at the molecular, metabolic, and cellular level. Our main finding is that early, but not late onset of ERT prevents an ovariectomy-associated increase in mitochondrial hydrogen peroxide levels, oxidative damage to lipids and proteins, and a decrease in glutathione peroxidase and catalase activity in rats. This may be due to a change in the estrogen receptor (ER) expression profile: ovariectomy increases the ER α/β ratio and immediate estrogen replacement prevents it. Positron emission tomography analysis shows that ovariectomy decreases the brain glucose uptake in vivo and that estrogen administration is beneficial, but only if administered immediately after deprivation. Ovariectomy decreases GLUT-1 and 3 glucose transporters in the brain, and only early onset estrogen administration prevents it. Plasma from rats treated with estrogens immediately after ovariectomy show similar metabolomics profiles as controls. We provide molecular basis for the recommendation of early onset ERT and explain its lack of effectiveness if a significant time period elapses after ovariectomy and probably after the onset of menopause. Only early, but not late onset administration of estrogens after ovariectomy has beneficial effects at molecular levels on oxidative stress, brain glucose uptake, and metabolomic profiles.

Preconditioning and post-treatment with cobalt chloride in rat model of perinatal hypoxic–ischemic encephalopathy

Background: Hypoxia–ischemia (HI)-induced perinatal encephalopathy is a major cause of acute mortality and chronic neurologic morbidities such as cerebral palsy, mental retardation, and epilepsy. As the essential transcription factor for the activation of hypoxia-inducible genes, hypoxia-inducible factor 1 alpha (HIF-1α) plays an important role in the pathophysiological response to the stress of HI brain damage. Whether HIF-1α activation promotes neuroprotection in HI tissues is controversial. Methods: The left common carotid artery of rats aged 7days was ligated under anesthesia. The pups were then exposed to hypoxia in a normobaric chamber filled with 8% oxygen and 92% nitrogen for 2.5h. In the sham control group, the left common carotid artery was exposed but was not ligated or exposed to hypoxia. To assess the time window for effective treatment, the HIF-1α inducer cobalt chloride (CoCl2) was injected subcutaneously 1day before surgery, immediately or 1day after surgery. The brain tissues were harvested from the pups of each groups at 1, 2 and 7days after insult for HIF-1α protein ant its target genes expression and for investigating the injury. Morris water maze tests were performed at postnatal 7weeks. Results: HIF-1α protein levels and its target genes vascular endothelial growth factor, heme oxygenase-1, and insulin-like growth factor 1 were markedly increased after intraperitoneal injection of CoCl2 (60mg/kg). The target gene inducible nitric oxide synthase exhibited a biphasic time course. HI caused apoptosis and reduced capillary density, which were ameliorated by CoCl2. Both preconditioning with CoCl2 24h before HI and administration of CoCl2 24h after HI improved long-term reference memory compared with that in vehicle-injected littermate controls. Administration of CoCl2 immediately after HI did not improve spatial working memory. Conclusions: CoCl2 activates HIF-1α and protects against brain damage in vivo. The time of administration could be used to manipulate the activity of HIF-1α pathways and promote recovery.

Protective effects of intraperitoneal injection of TAT-SOD against focal cerebral ischemia/reperfusion injury in rats

Aims The intracellular superoxide anion has been shown to be involved in brain injury. TAT-Superoxide dismutase (TAT-SOD) can be transduced across the cell membrane to scavenge superoxide. This protein's unique properties make it a promising therapeutic candidate to attenuate cerebral damage. In this study, we sought further the understanding of the fusion protein's cerebral protective effects and the mechanism which is exerted in these effects. Main methods Male Sprague Dawley rats (n = 100, 230 ± 20 g) were divided randomly into five experimental groups: a sham group, a cerebral Ischemia/Reperfusion (I/R) group treated with saline (20 ml/Kg, i.p.), and three cerebral I/R groups treated with TAT-SOD (25 KU/ml/Kg, i.p.) at either 2 h before I/R, 2 h after I/R or 4 h after I/R. Cerebral I/R injury was facilitated by inducing ischemia for two hours followed by 24 h reperfusion. The levels of SOD, Malondialdehyde (MDA), and ATPase in cerebral tissues were determined. The apoptotic indexes were evaluated, and apoptosis genes were analyzed immunohistochemically. Key findings TAT-SOD treatment significantly increased cerebral SOD and ATPase activities, decreased MDA content, and remarkably reduced apoptosis indexes. TAT-SOD treatments 2 h before or after I/R significantly reduced caspase-3 and bax proteins and boosted bcl-2 protein, while the treatment at 4 h after I/R showed no influence on the three proteins. Significance TAT-SOD treatment effectively enhanced cerebral antioxidant ability, reduced lipid peroxidation, preserved mitochondrial ATPase and thus inhibited nerve cell apoptosis. The effective treatment window extended from 2 h before to 2 h after I/R.

Are intra-tympanically administered steroids effective in patients with sudden deafness? Implications for current clinical practice

Over 60 years since its first report, sudden sensorineural hearing loss (SSNHL) still represents an ill-explained condition, with potentially devastating effects for the quality of life of previously well patients. The present study critically reviewed the available evidence regarding the efficacy of intra-tympanic steroid administration in the treatment of SSNHL. Factors affecting that efficacy were also explored. The literature was systematically reviewed in Medline and other database sources until July 2011, and analyzed through critical analysis of pooled data. The study selection included multi-center prospective randomized control trials, prospective randomized comparative, prospective comparative and prospective studies, retrospective comparative and retrospective studies. The total number of analyzed studies was 43. Intra-tympanic steroids appear to be effective as primary (strength of recommendation A), or salvage treatment (strength of recommendation B) in SSNHL. It is difficult to draw definite conclusions regarding the efficacy of combination therapy. The identification of a time window for effective treatment in the former two approaches yields a grade C strength of recommendation. Primary intra-tympanic treatment is the most effective modality in terms of complete hearing recovery (34.4% cure rate). There is not enough evidence to attribute treatment failures to impaired permeability of the round window membrane. Most complications of intra-tympanic treatment are minor, temporary, and conservatively managed. Intra-tympanic steroids can theoretically provide a more organ-specific treatment in patients with SSNHL. The observation that they seem effective both as primary and salvage treatment modalities with a very low complication rate may have serious implications for current clinical practice.

Management of acute stroke: impact of registration studies.

Stroke is a life-threatening or life-changing disease that is expensive in health care costs and lost productivity. Stroke also is a leading cause of human suffering. While the risk of stroke may be reduced with advances in prevention, recent advances in acute care can limit the consequences of stroke. In particular, the success of reperfusion therapies including intra-arterial interventions and intravenous administration of thrombolytic agents means that some patients with stroke may be cured. Still, the time window for effective treatment of stroke is relatively short. As a result, modern stroke management requires the close collaboration of the public, health care providers, administrators, insurance companies, and the government. Potential strategies to extend modern stroke care to as many patients as possible include 1) educational programs to train community emergency medical service personnel and physicians, 2) development of stroke care plans at community hospitals, 3) an integrated community-comprehensive stroke center program based on consultation, and telemedicine. The goal is to have a highly integrated approach to provide emergency treatment of the stroke that provides key emergency treatment, including intravenous administration of thrombolytic medications, at a community hospital (primary stroke center) with evacuation to a comprehensive stroke center that has resources and expertise that are not available in the primary stroke center. Taiwan is an ideal location for the development of such regional stroke programs.

Neurodevelopment and executive function in autism

Autism is a neurodevelopmental disorder characterized by social and communication deficits, and repetitive behavior. Studies investigating the integrity of brain systems in autism suggest a wide range of gray and white matter abnormalities that are present early in life and change with development. These abnormalities predominantly affect association areas and undermine functional integration. Executive function, which has a protracted development into adolescence and reflects the integration of complex widely distributed brain function, is also affected in autism. Evidence from studies probing response inhibition and working memory indicate impairments in these core components of executive function, as well as compensatory mechanisms that permit normative function in autism. Studies also demonstrate age-related improvements in executive function from childhood to adolescence in autism, indicating the presence of plasticity and suggesting a prolonged window for effective treatment. Despite developmental gains, mature executive functioning is limited in autism, reflecting abnormalities in wide-spread brain networks that may lead to impaired processing of complex information across all domains.