Impact of a novel pre-hospital stroke notification programme on acute stroke care key performance indicators in Hong Kong: a multicentre prospective cohort study with historical controls.

INTRODUCTION: Early identification and initiation of reperfusion therapy is essential for suspected acute ischaemic stroke. A pre-hospital stroke notification (PSN) protocol using FASE (facial drooping, arm weakness, speech difficulties, and eye palsy) was implemented to improve key performance indicators (KPIs) in acute stroke care delivery. We assessed KPIs and clinical outcomes before and after PSN implementation in Hong Kong. METHODS: This prospective cohort study with historical controls was conducted in the Accident and Emergency Departments of four public hospitals in Hong Kong. Patients were screened using the PSN protocol between August 2021 and February 2022. Suspected stroke patients between August 2020 and February 2021 were included as historical controls. Door-to-needle (DTN) and door-to-computed tomography (DTC) times before and after PSN implementation were compared. Clinical outcomes including National Institutes of Health Stroke Scale score at 24 hours and modified Rankin Scale score at 3 months after intravenous recombinant tissue-type plasminogen activator (IV-rtPA) were also assessed. RESULTS: Among the 715 patients (266 PSN and 449 non-PSN) included, 50.8% of PSN patients and 37.7% of non-PSN patients had a DTC time within 25 minutes (P<0.001). For the 58 PSN and 134 non-PSN patients given IV-rtPA, median DTN times were 67 and 75.5 minutes, respectively (P=0.007). The percentage of patients with a DTN time within 60 minutes was higher in the PSN group than in the non-PSN group (37.9% vs 21.6%; P=0.019). No statistically significant differences in clinical outcomes were observed. CONCLUSION: Although the PSN protocol shortened DTC and DTN times, clinical outcomes did not significantly differ.

Visual search performance in infants associates with later ASD diagnosis.

An enhanced ability to detect visual targets amongst distractors, known as visual search (VS), has often been documented in Autism Spectrum Disorders (ASD). Yet, it is unclear when this behaviour emerges in development and if it is specific to ASD. We followed up infants at high and low familial risk for ASD to investigate how early VS abilities links to later ASD diagnosis, the potential underlying mechanisms of this association and the specificity of superior VS to ASD. Clinical diagnosis of ASD as well as dimensional measures of ASD, attention-deficit/hyperactivity disorder (ADHD) and anxiety symptoms were ascertained at 3 years. At 9 and 15 months, but not at age 2 years, high-risk children who later met clinical criteria for ASD (HR-ASD) had better VS performance than those without later diagnosis and low-risk controls. Although HR-ASD children were also more attentive to the task at 9 months, this did not explain search performance. Superior VS specifically predicted 3 year-old ASD but not ADHD or anxiety symptoms. Our results demonstrate that atypical perception and core ASD symptoms of social interaction and communication are closely and selectively associated during early development, and suggest causal links between perceptual and social features of ASD.

Inversion symmetry breaking induced triply degenerate points in orderly arranged PtSeTe family materials.

k paths exactly with [Formula: see text] symmetry allow to find triply degenerate points (TDPs) in band structures. The paths that host the type-II Dirac points in PtSe2 family materials also have the [Formula: see text] spatial symmetry. However, due to Kramers degeneracy (the systems have both inversion symmetry and time reversal symmetry), the crossing points in them are Dirac ones. In this work, based on symmetry analysis, first-principles calculations, and [Formula: see text] method, we predict that PtSe2 family materials should undergo topological transitions if the inversion symmetry is broken, i.e. the Dirac fermions in PtSe2 family materials split into TDPs in PtSeTe family materials (PtSSe, PtSeTe, and PdSeTe) with orderly arranged S/Se (Se/Te). It is different from the case in high-energy physics that breaking inversion symmetry I leads to the splitting of Dirac fermion into Weyl fermions. We also address a possible method to achieve the orderly arranged in PtSeTe family materials in experiments. Our study provides a real example that Dirac points transform into TDPs, and is helpful to investigate the topological transition between Dirac fermions and TDP fermions.

Outbreak of human metapneumovirus infection in psychiatric inpatients: implications for directly observed use of alcohol hand rub in prevention of nosocomial outbreaks.

Nosocomial outbreaks of infectious diseases in psychiatric facilities are not uncommon but the implementation of infection control measures is often difficult. Here, we report an outbreak of an acute respiratory illness in a psychiatric ward between 29 July and 20 August 2005 involving 31 patients. Human metapneumovirus was detected in seven (23%) patients by reverse transcription-polymerase chain reaction and nucleotide sequencing. A review of outbreak surveillance records showed that six nosocomial outbreaks occurred in the year 2005, of which four (67%) were confirmed or presumably related to a respiratory viral infection. Directly observed deliveries of alcohol hand rub 4-hourly during daytime to all psychiatric patients was instituted in December 2005. Only one nosocomial respiratory viral outbreak occurred in the following year. The total number of patients and staff involved in nosocomial outbreaks due to presumed or proven respiratory virus infections decreased significantly from 60 to six (P<0.001), whereas those due to all types of nosocomial outbreaks also decreased from 70 to 24 (P=0.004). Alcohol hand rub has been shown to have potent bactericidal and virucidal activity against a wide range of nosocomial pathogens. Regular use of directly observed alcohol hand rub may decrease the incidence and scale of nosocomial outbreaks due to enveloped respiratory viruses especially in mentally incapacitated patients.

Embryogeneic cell type, organ site sequence specificity in human cancers.

An extensive series of cross-hybridization studies were carried out with the DNA-RNA molecular hybridization technique. Molecular 70 S [3H]DNA probes synthesized from human central nervous system, gastrointestinal, pulmonary, and prostatic carcinomas were hybridized to cytoplasmic RNA's isolated from cancers of virtually all organ sites of the human body. Results indicated sequence homology between cancers of the same organ or cell type but not with cancers of different cell types. Thus cell types based on embryological origins determine the organ site specificity of the involved sequences. The designation of 70 S [3H]DNA denotes those [3H]DNA's that were copied off the template 70 S RNA, as distinguished from total [3H]DNA product, which includes all DNA's synthesized. It does not necessarily follow nor is it to be inferred that the 70 S [3H] DNA thus designated contains the full complement of the sequences found in the 70 S RNA template.

YM155 down-regulates survivin and XIAP, modulates autophagy and induces autophagy-dependent DNA damage in breast cancer cells.

BACKGROUND AND PURPOSE: The aim of this study was to determine the potency and molecular mechanism of action of YM155, a first-in-class survivin inhibitor that is currently under phase I/II clinical investigations, in various drug-resistant breast cancers including the oestrogen receptor positive (ER(+) ) tamoxifen-resistant breast cancer and the caspase-3-deficient breast cancer. EXPERIMENTAL APPROACH: The potency of YM155 in SK-BR-3, MDA-MB-231, MCF7 and its tamoxifen-resistant sublines, TamR6, TamR7, TamR8, TamC3 and TamC6, were determined by MTT assay. Western blot analysis, flow cytometric analysis, reverse transcription-PCR, fluorescent microscopy and comet assay were used to determine the molecular mechanism of action of YM155 in different breast cancer cell lines. KEY RESULTS: YM155 was equally potent towards the parental ER(+) /caspase-3-deficient MCF7 breast cancer cells and its tamoxifen-resistant sublines in vitro. The ER(-) /HER2(+) SK-BR-3 breast cancer cells and the triple-negative/caspase-3-expressing metastatic aggressive MDA-MB-231 breast cancer cells were also sensitive to YM155 with IC50 values in the low nanomolar range. Targeting survivin by YM155 modulated autophagy, induced autophagy-dependent caspase-7 activation and autophagy-dependent DNA damage in breast cancer cells. Interestingly, YM155 also induced XIAP degradation and the degradation of XIAP might play an important role in YM155-induced autophagy in breast cancer cells. CONCLUSIONS AND IMPLICATIONS: YM155 is a potent survivin inhibitor that has potential for the management of various breast cancer subtypes regardless of the expression of ER, HER2 and caspase-3. Importantly, this study provides new insights into YM155's molecular mechanism of action and therapeutic potential in the treatment of tamoxifen-resistant breast cancer.

Rabbit sex hormone binding globulin: primary structure, tissue expression, and structure/function analyses by expression in Escherichia coli.

Sex hormone binding globulin (SHBG) is a homodimeric plasma protein found in mammals that binds sex steroids with high affinity and regulates their bioavailability. The protein is identical in structure and properties to the androgen binding protein (ABP) found in the male reproductive tract. We have isolated a 1245-base pair rabbit SHBG cDNA encoding a reading frame for a signal peptide followed by a protein of 367 amino acids, which shares 79.0, 68.1 and 63.2% amino acid identity with the corresponding human, rat and mouse proteins respectively. Northern blot and hot-nested PCR analyses indicated that rabbit SHBG is produced from a 1.6 kilobase mRNA in the liver of both sexes and in the testis. The rabbit SHBG cDNA was inserted into pGEX-1 lambda T for expression of a glutathione S-transferase/SHBG fusion protein in Escherichia coli. The bacterial product bound 5 alpha-dihydrotestosterone (DHT) in the same manner as the corresponding protein in serum. The dissociation constants (Kd) for rabbit and human SHBGs produced in E. coli were 11.1 +/- 1.1 nM and 2.1 +/- 0.6 nM respectively, and rabbit SHBG formed a less stable protein-steroid complex (t1/2 = 5 min) than human SHBG (t1/2 > 60 min). Unlike human SHBG, rabbit SHBG does not bind estradiol with high affinity. To aid in the identification of differences in the sequences of rabbit and human SHBG, which determine species differences in steroid-binding affinity and specificity, chimeras containing the 5'-terminal half of SHBG from one species and 3'-terminal half of SHBG from the other species were constructed and expressed. It was found that the chimeric proteins assumed similar steroid-binding affinity and specificity as the wild-type proteins when the amino (N)-terminal half of SHBG was derived from the same species. Replacement of the carboxyl (C)-terminal half of rabbit SHBG by the corresponding region of the human molecule increased the integrity of its steroid-protein complex. This supports the concept that amino acids within the N-terminal half of SHBG constitute the steroid-binding domain while the C-terminal half of the molecule may provide structural stability to the protein and its steroid-binding site.

Recent advances in anti-survivin treatments for cancer.

Apoptosis occurs via extrinsic or intrinsic signalling each triggered and regulated by many different molecular pathways. In recent years, the selective induction of apoptosis through survivin in tumour cells has been increasingly recognized as a promising approach for cancer therapy. Survivin has multiple functions including cytoprotection, inhibition of cell death, and cell-cycle regulation, especially at the mitotic process stage, all of which favour cancer survival. Many studies on clinical specimens have shown that survivin over expression is invariably up regulated in human cancers, associated with resistance to chemotherapy or radiation therapy, and linked to poor prognosis, suggesting that cancer cells survive with survivin. On the basis of these findings, survivin has been proposed as an attractive target for new anticancer interventions. Survivin inhibitors recently entered clinical trials. Recent studies suggest a possible role for survivin in regulating the function of normal adult cells. However, the expression and function of survivin in normal tissues are still not well characterized and understood. Still better understandings of survivin's role in tumour versus normal cells are needed for designing the strategies to selectively disrupt survivin in cancers. In the present review, we summarise the importance of recent survivin-targeted cancer therapy for future clinical application.

The correlation between craniovertebral angle, backpack weights, and disability due to neck pain in adolescents.

PURPOSES: To investigate the responses of the craniovertebral (CV) angle to backpack loadings in adolescents with and without neck pain and to explore the relationships between CV angle, relative backpack weight, neck pain and disability. METHODS: A cross-sectional single-blinded study was conducted on 60 adolescents (30 neck pain and 30 non-neck pain) aged from 13 to 18 years old. The verbal analog scale (VAS) and Chinese version of Northwick Park Neck Pain Questionnaire (NPQ) were used to assess neck pain severity and disability respectively. CV angle was measured in neutral and with backpack loadings of 5% to 30% of subject's body weight by using the Head Posture Spinal Curvature Instrument (HPSCI). RESULTS: In both groups, CV angles gradually decreased with increment of backpack loadings and the amount of decreases became significant from 10% body weight onwards (P < 0.05). Although the changes of CV angles did not show any significant differences at any point of comparison between the groups, the neck pain group showed a clinically significant decrease of CV angle (∼ 5°) at 10% relative loading whereas non-neck pain group did it at 15% relative loading. Change of CV angles did not show significant correlations with relative backpack weight, cervical pain and disability (P > 0.05). CONCLUSIONS: Our findings suggested a safety limit of 10% relative backpack load for adolescents. The results showed the tendency that the ability of maintaining good head posture in response to backpack loadings by non-neck pain subjects might be better than those with neck pain.

The correlation between craniovertebral angle, backpack weights, and disability due to neck pain in adolescents.

PURPOSES: To investigate the responses of the craniovertebral (CV) angle to backpack loadings in adolescents with and without neck pain and to explore the relationships between CV angle, relative backpack weight, neck pain and disability. METHODS: A cross-sectional single-blinded study was conducted on 60 adolescents (30 neck pain and 30 non-neck pain) aged from 13 to 18 years old. The verbal analog scale (VAS) and Chinese version of Northwick Park Neck Pain Questionnaire (NPQ) were used to assess neck pain severity and disability respectively. CV angle was measured in neutral and with backpack loadings of 5% to 30% of subject's body weight by using the Head Posture Spinal Curvature Instrument (HPSCI). RESULTS: In both groups, CV angles gradually decreased with increment of backpack loadings and the amount of decreases became significant from 10% body weight onwards (P < 0.05). Although the changes of CV angles did not show any significant differences at any point of comparison between the groups, the neck pain group showed a clinically significant decrease of CV angle ( approximately 5 degrees ) at 10% relative loading whereas non-neck pain group did it at 15% relative loading. Change of CV angles did not show significant correlations with relative backpack weight, cervical pain and disability (P > 0.05). CONCLUSIONS: Our findings suggested a safety limit of 10% relative backpack load for adolescents. The results showed the tendency that the ability of maintaining good head posture in response to backpack loadings by non-neck pain subjects might be better than those with neck pain.

Structural requirements for the functional activity of a U1 snRNA gene enhancer.

The transcriptional enhancer of a chicken U1 small nuclear RNA (snRNA) gene contains a GC-box, an octamer motif, and an SPH motif that are recognized by the transcription factors Sp1, Oct-1, and SBF respectively. Previous work indicated that the octamer and the SPH motifs were both required for U1 gene enhancer activity in frog oocytes when the U1 gene was coinjected with a competing snRNA gene template. Here we show that neither two copies of the octamer motif, nor two copies of the SPH motif, can effectively substitute for the natural combination of octamer and SPH. Furthermore, neither the octamer nor the SPH motif (in the absence of the other) functioned efficiently in combination with a GC-box. Alteration of the spacing between the octamer and SPH motifs also reduced U1 template activity. Several potential cis-acting elements other than the SPH motif, with one possible exception among those tested, were unable to cooperate with the octamer motif to effectively enhance U1 gene expression. These results indicate that rather stringent structural requirements exist with respect to the essential cis-acting motifs present in the U1 enhancer, possibly reflecting the unique properties of the transcription complexes assembled on snRNA gene promoters.

Molecular evidence of viral-like biochemical activities in human genitourinary malignancies.

We have demonstrated previously that core structures of urine samples from patients with genitourinary malignancies contain ribonucleic acid-directed deoxyribonucleic acid polymerase and a high molecular weight ribonucleic acid. If these particles originated from the existing genitourinary malignancies then the malignancies should contain similar characteristics. We examined 13 prostatic carcinomas, 4 bladder carcinomas, 1 urethral carcinoma and 1 hypernephroma. Positive reactions were noted in 10 of the 13 prostatic carcinomas (77 per cent), all 4 bladder carcinomas, the 1 urethral carcinoma and the hypernephroma with the simultaneous detection assay. The control samples consisted of 7 tissues of benign prostatic hypertrophy, and tissue from 2 normal bladders and 1 normal kidney. None of these tissues showed a positive response. Tritium labeled deoxyribonucleic acid probes synthesized from the malignant tissues hybridized to the polysomal ribonucleic acids but not to the corresponding normal tissues. Particles derived from the probes have a density of 1,1620 in sucrose gradient. No sequence homology could be demonstrated with various known oncogenic ribonucleic acid viruses nor with malignancies arising from other organs.

Biochemical evidences for ribonucleic acid viral-like characteristics in malignant diseases of gastrointestinal tract and lung in humans.

It has been demonstrated that malignant diseases of the gastrointestinal tract and lung in humans possess three characteristics invariably found in ribonucleic acid tumor viruses: the presence of a ribonucleic acid directed deoxyribonucleic acid polymerase, reverse transcriptase; a high molecular weight ribonucleic acid with a sedimentation coefficient of 70 Svedberg units, and particulate elements with densities of 1.16 to 1.18 grams per milliliter sucrose gradient. Twelve of 17 carcinomas of the colon, three of five carcinomas of the stomach, all three carcinomas of the rectum and seven of ten carcinomas of the lung displayed detectable evidence of these viral-like entities. None of the corresponding normal tissues had positive reactions.

Detection of viral-like cores from the urine of patients with genito-urinary malignancies.

Simultaneous detection assays on the core structures derived from the cerebrospinal fluid samples of patients with various types of central nervous system tumors have demonstrated the feasibility of this technique in detecting some of the diagnostic features of RNA tumor viruses. Similar assays done on urine samples from patients iwth various types of tumors in their genitourinary tracts have shown that of the 18 such samples from tumor patients, 15 or 83% were found to be positive. The control samples consisted of three from patients with benign prostatic hypertrophy and four from normal persons. None of these gave a positive reaction. [3H]DNA probes synthesized from the core structures from them hybridized readily to their corresponding polysomal RNAs but no to control tissues. The densities of particles from these samples have been found to be 1.168 g/ml for bladder carcinoma and 1.165 for prostatic carcinoma, the same densities as those found RNA tumor viruses.

Peripartum tuberculosis as a form of immunorestitution disease.

The aim of this study was to assess the clinical spectrum of peripartum tuberculosis from the perspective of immunorestitution disease. Of 29 patients with peripartum tuberculosis, 27 (93.1%) had extrapulmonary tuberculosis, 20 (69%) of whom were affected in the central nervous system. Twenty-two (75.9%) patients had no clinical features suggestive of tuberculosis during pregnancy. The median time from delivery to the onset of immunorestitution was 4 days, but treatment with anti-tuberculous therapy was delayed for a median time of 27 days after the onset of symptoms. Despite therapy, 11 (38%) patients died and 4 (13.8%) had residual functional deficits. Peripartum tuberculosis is an important differential diagnosis of postpartum fever (of unknown origin) without localized signs.