Pattern Of Arrest Research Articles

Circadian variation pattern of sudden cardiac arrest occurred in Chinese community

BackgroundThe circadian variation pattern of sudden cardiac arrest (SCA) occurred in Chinese community including both community healthcare centres and primary hospitals remains unknown. This study analysed the circadian variation of...

Blastocyst formation is similar in obese and normal weight women: a morphokinetic study.

Does the embryo cleavage pattern and rate of blastocyst formation differ between normal weight and obese women undergoing IVF? Embryo morphokinetic development, final blastocyst formation rate and blastocyst morphology do not differ between obese and normal weight women. Female obesity has been related to impaired IVF outcomes. Although the mechanisms responsible for this detrimental effect are thought to include impaired oocyte and embryo quality and reduced endometrial receptivity, they are yet to be confirmed. Embryo quality has been commonly assessed using static morphological criteria. Only three studies have analysed the progress of embryos up to the blastocyst stage in women with elevated BMI, but they have used small samples of patients or have obtained contradictory results. This retrospective, cohort study, was performed from January 2016 to May 2020. A total of 3316 ICSI cycles from 2822 women were included, of which 1251 cycles were part of a preimplantation genetic testing programme. In total, 17 848 embryos were analysed. This study reports on the IVF cycles of infertile women, with a known BMI, who underwent ICSI and whose embryos were grown until the fifth/sixth day of development in a time-lapse system. Patients were grouped as follows. Underweight was defined as a BMI <18.5 kg/m2; normal weight was a BMI of 18.5-24.9 kg/m2; overweight was a BMI of 25-29.9 kg/m2; and obesity was a BMI of ≥30 kg/m2. Embryo development was assessed on an external computer with analysis software. Despite an initial slower pattern of embryo development, the blastocyst formation rate on day 5 or on day 5 plus day 6 did not differ in obese women with respect to the other three BMI groups. Moreover, based on the evaluation of inner cell mass and the trophectoderm on both days of blastocyst development, embryo quality was similar across the BMI groups, as were the pattern of development and arrest up to blastocyst formation and the distribution of the categories of full, expanded and hatching blastocysts. Limitations include the retrospective analysis of data, the use of BMI as the only parameter to define normal/abnormal female body weight, and the lack of complete information about clinical outcomes. Blastocyst formation and embryo morphokinetics are not affected by female obesity, and the poorer IVF outcomes described for such women are probably due to deficient endometrial receptivity. The role of endometrial progesterone exposure on the day of embryo transfer should be analysed in future studies as a possible determining factor. No external funding was used and there are no competing interests. N/A.

BLASTOCYST FORMATION IS NOT AFFECTED BY FEMALE OBESITY: A MORPHOKINETIC STUDY

To determine whether the embryo cleavage pattern and the rate of blastocyst formation differs between normal weight and obese women undergoing in vitro fertilization (IVF) with ICSI (intracytoplasmic sperm injection). This is a retrospective cohort study performed from January 2016 to May 2020 in IVIRMA-Valencia. A total of 3,316 ICSI cycles from 2,822 women were included, with 1,251 cycles belonging to the Preimplantation Genetic Testing (PGT) program. Patients were grouped according to their body mass index (BMI).Underweight was defined as a BMI < 18.5 kg/m2 (n = 173 cycles from 140 women), normal weight as a BMI of 18.5–24.9 kg/m2 (n= 2,339 cycles from 1,989 women), overweight as a BMI of 25–29.9 kg/m2(n = 643 cycles from 548 women) and obesity as a BMI of >30 kg/m2 (n =161 cycles from 145 women).All embryos were grown in vitro until the fifth or sixth day in a time-lapse system - EmbryoScope, EmbryoScope Plus (Vitrolife) and Geri Plus (GeneaBiomedx) - and its development was assessed on an external computer with a specific software for the purpose. There were no differences in sperm parameters or male age among the four BMI groups. Underweight women were l year or less younger than the other three groups. The percentage of women with polycystic ovary syndrome was higher but not significantly different in the obese group. Indications for PGT do not differ among groups .The number of oocytes retrieved or mature oocytes microinjected was significantly higher in the obese group than in the normal weight group. However, fertilization rates and number of embryos transferred were similar in the four BMI groups. A higher percentage of surplus embryos for freezing was observed in the underweight group when compared to normal weight women. All the embryos were transferred or frozen in blastocyst stage. Despite an initial slower pattern of embryo development, the final blastocyst formation rate in day 5 or in day 5 plus day 6 did not differ in obese women when compared to the other BMI groups. Moreover, embryo quality, based on the evaluation of inner cell mass and trophectoderm in both days of blastocyst development was similar across BMI groups. The same was observed with respect to the pattern of development and arrest up to blastocyst formation and the different categories of full, expanded and hatching blastocysts. Blastocyst formation is not affected by female BMI.

West syndrome - epileptic encephalopathy at early infancy

West syndrome (WS), synonymously infantile spasm or epileptic spasm, is a rare type of epileptic encephalopathy occurring at early infancy that exists with variable life expectancy. It is the most common form of epileptic encephalopathy. WS presents with spasms marked by extensor or mixed movements with distinct electroencephalogram (EEG) pattern of hypsarrhythmia, flexor and psychomotor arrest. Children with west syndrome always depict abnormal EEG, but sometimes the abnormality is seen only during sleep. The incidence of infantile spasms is found closer to 1 in 2,000 children, that typically begins between 2-12 months of age and peaks between 4-8 months of age. It is observed in otherwise healthy infants and also among infants with abnormal cognitive development. If this spasm happens in older subjects, they are preferably called "epileptic spasms" rather than infantile spasms. The goal for treatment of infantile spasms is to have complete control of spasms. Hormonal therapy with ACTH or vigabatrin is the mainstay of treatment. In spite of the development of new antiepileptic drugs (AEDs), about 35-40% of cases are drug-resistant. Children affected with the west syndrome can be cured, but a successful therapy often depends on the timely diagnosis. This case report is one evidence highlighting the treatment strategy for the west syndrome, and this could be useful for any further study regarding this topic.

Age pattern of gestational arrest in India and its regions: Evidence from NFHS-4 (2015–2016)

IntroductionPregnancy loss is a public health issue throughout the world. Miscarriage and induced abortion are the two main dimensions of pregnancy loss. The prevalence of early pregnancy loss due to miscarriage and abortion is mostly unknown due to the lack of early registration of pregnancies in most places, and especially in low- and middle-income countries. In a country like India, not enough attempts have been made to recognize pregnancy loss by weeks of gestational age. ObjectiveThis study aims to know about the age-pattern of gestational termination using the calendar information from the fourth round of the National Family Health Survey. Statistical MethodsA generalized linear model with a binomial distribution assumption and Kaplan-Meier survival model with left truncation was used for statistical analysis. ResultsThe age-pattern of miscarriage produces a vertical convex shape curve when age is drawn at y-axis and the miscarriage rate at x-axis. There is a high relative risk of miscarriage to women age below 20 years and age 35 years onwards, whereas abortion risk was high among women age 30 and above years. Among women age 15–19 years, the abortion rate at 27 abortions per thousand pregnancies was the highest in the northeast region, and the miscarriage rate at 67 miscarriages per thousand pregnancies was estimated to be the highest in the western region among all the regions. A sizeable proportion of miscarriages and induced abortions also occurred in the second trimester and all the region. ConclusionThis article brings out that miscarriage is more commonly prevalent among women in the adolescence age 15–19 years and in the latter half of the reproductive span, whereas the incidence of abortion increases with age. The western and the northeast regions registered maximum miscarriage and abortion rates among women age 15–19, respectively. The central region as a whole showed the highest rate of miscarriage, whereas the abortion rate was the highest in the northeast region in India. The findings of the study will be beneficial in making appropriate policy provisions for postponing pregnancies among women in their adolescence and preventing the occurrence of miscarriages among more vulnerable age groups of women and regions by providing a complete package of high-quality antenatal care services.

Intensive Care Unit Approach to the Diagnosis of Brain Death in Infratentorial Neurologic Pathology: Case Reports

The ischemic and primary vascular injury of the brainstem (BS) can determine, among other serious conditions, the brain death (BD) of the individual. We present 2 cases of individuals with primary ischemic vascular disease of the BS who evolved to BD and were donors of solid organs and tissues. In both cases, the clinical examination was positive for the diagnosis of BD, and transcranial Doppler did not confirm the pattern of cerebral circulatory arrest that accompanies BD. The magnetic resonance angiography performed on 1 patient confirmed the lesion etiology and the presence of vascular obstruction. Both patients were real and effective organ and tissue donors. In these cases, we suggest not to resort to transcranial Doppler as an auxiliary diagnostic test.

Timor Deer (Cervus Timorensis) Arrest System Marind People with Tidal Local Wisdom

Deer are wildlife that has economic value because it can produce meat, leather, and velvet (young horn). Deer populations in nature have decreased due to uncontrolled wild poaching and damage to habitat. Indonesia has five types of deer, i.e., Cervus unicolor, Cervus timorensis, Axis kuhlii, Muntiacus Muntjak, and Axis axis (deer total). However, deer in Indonesia that have the opportunity to be empowered, there are several types, namely Cervus timorensis, Cervus unicolor and Axis axis, and in Merauke, especially in the had tribe0 has its distinctive characteristic in the process of catching deer. The purpose of the study was to know the pattern of deer arrest by the Malind tribe. The method used in this research is to conduct surveys and Wawan ways as well as observation of the field, the data in the analysis in a descriptive approach to conclude the investigation. The results showed that the pattern of deer caught in the Marind tribe traditionally done with snares, bamboo rinsing, as well as patterns carried out covering the forest burning Sawvana in the dry season of the cattle, besieged fire and dwelling on the land, and the season The community rained to the deck area (dense forest) that became the deer's dwelling and avoided the puddle of the sea, and the community captured it quickly. The chance of this research is the process of catching deer, in general, is done by the had in 2 ways that in the summer by burning and drought with the trap system.

Abstract 2307: Differential effects of N-terminal vs C-terminal truncating CDKN1A mutations on cisplatin resistance in bladder cancer

Abstract Introduction Approximately 15% of muscle invasive bladder cancers harbor mutations in the CDKN1A gene, which encodes the p53 target gene p21, with the majority of alterations truncating the peptide. We previously found that proximal truncation of p21 sensitized cells to cisplatin, while distal truncations made them more resistant. We hypothesized that truncations preserving the CDKi domain but ablating the PCNA binding domain would abrogate p21's ability to sequester PCNA but maintain cell cycle arrest capacities, enhancing the interaction between mono-ubiquitiniated-PCNA (ub-PCNA) and DNA polymerase eta (Pol η), resulting in increased TLS and DNA damage tolerance. Methods We used SW780 cell line for this study based on its resistance to cisplatin and p53 and p21 WT status. CRISPR sgRNAs designed to target amino acids 12 and 109 (SW780-sg12 and SW780-sg109) were used to introduce frameshifts and disrupt the majority of the peptide or only the PCNA the binding domain, respectively. sgRNA designed to target GFP was used as a control (sgGFP). We treated the cells with GI50 dose of cisplatin and analyzed post-cisplatin cell-cycle profile over 96 hours using PI-FACS and immunoblot. We treated all three cell types with increasing doses (0-40 μM) of cisplatin for 24 hours and measured the levels of ub-PCNA (K164) and Pol η using immunoblot. Results SW780-sgGFP arrested in S-phase at 48 and 72 hours but overcame this arrest at 96 hours and began to cycle again. SW780-sg12 were unable to arrest in S-phase, whereas SW780-sg109 were able to arrest in S-phase at 48 to 96 hours. This pattern of S-phase arrest was further confirmed by prolonged upregulation of cyclin D1 in SW780-sg109 and brief upregulation in SW780-sgGFP. ub-PCNA and Pol η accumulated in a dose responsive manner in all three cell types at 24 hours after cisplatin treatment. ub-PCNA increased abruptly at higher cisplatin doses in SW780-sgGFP, whereas the increase was gradual in CDKN1A-edited cells. Interestingly, in SW780-sg109, Pol η induction was strongest at all doses. Conclusion Cisplatin causes S-phase arrest in SW780-sgGFP cells, possibly by inducing replicative stress. However, this arrest is eventually bypassed and the cells progress through the cell cycle. S-phase arrest is not possible in the absence of a functioning p21, indicating that p21 plays a vital role in bringing about post-cisplatin cell cycle arrest. Interestingly, truncated p21 with intact CDKi domain is capable of causing stronger and more prolonged S-phase arrest compared to the full-length peptide. TLS may play a role in DNA damage tolerance in SW780 cells as indicated by elevated ub-PCNA and pol η. Stronger accumulation of Pol η in SW780-sg109, possibly enhances TLS and thus cisplatin resistance. Moving forward, we would like to confirm the anticipated competition between p21 and Pol η for PCNA and further verify this phenomenon in other bladder cancer cell lines. Citation Format: Rahmat K. Sikder, Wafik S. El-Deiry, Philip H. Abbosh. Differential effects of N-terminal vs C-terminal truncating CDKN1A mutations on cisplatin resistance in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2307.

Case report of west syndrome: a rare severe epilepsy in infants

West syndrome (WS) also known as infantile spasms, is severe form of epilepsy of early childhood was first describe in 1840s. WS presents with myoclonic-tonic seizures (spasms) characterized by flexor, extensor or mixed movements with distinct electroencephalogram (EEG) pattern of hypsarrthmia and psychomotor arrest. Prevalence rate is ~ 4.0 cases per 10,000 children. Peak age of beginning is between 3 and 7 months; onset after 18 months is rare. Recent guidelines from the American Academy of Neurology and the Child Neurology Society for medical treatment of WS, recommends that ACTH is probably effective and vigabatrin is possibly effective in cessation of spasms of hypsarrhythmia. Although discovered 160 years ago, still its diagnosis, assessment and management continue to create many challenges to health care professionals and affected families. In this case of a 3 yr old male child was admitted for long period of almost 2 months before being discharged. This case was confirmed early but due to its complexity it took long time to get complete resolve of situation. ACTH with Valproate was found to effective; though ACTH showed some reactions still it was considered the best available medicine for WS. In conclusion, early detection and referral to a pediatric neurologist for clinical evaluation and prompt effective treatment is strongly recommended as it may improve prognosis.

Antenatal Diagnosis of Prune Belly Syndrome

AbstractPrune belly syndrome (PBS) is a rare congenital abnormality characterized by classical triad of urinary tract abnormalities, deficient abdominal musculature, and bilateral cryptorchidism. We present a prenatally diagnosed case of PBS identified at 12 weeks. Antenatal ultrasound study showed fetal bladder and abdomen to be enormously enlarged filling up whole of fetal abdomen with bilateral clubfeet. Gross examination showed very thin parchment-like defective anterior abdominal wall with protrusion of the abdominal contents. Microscopic examination showed hypoplasia of the abdominal muscle with overlying thin layer of epidermis. The histopathology examination of the abdominal wall muscles demonstrates a pattern of developmental arrest rather than one of atrophy consequent to early and severe obstruction. There is also absence of aponeurotic layer. Antenatal suspicion of PBS was corroborated on postnatal gross examination of the fetus and further confirmed on histopathological examination of the fetus.

Effects of combination therapy of docetaxel with selenium on the human breast cancer cell lines MDA-MB-231 and MCF-7.

PurposeThe anticancer property and cytoprotective role of selenium in chemotherapy have been reported. However, the combination effects of selenium on chemotherapy for advanced breast cancer have not yet been clearly defined. The purpose of this study was to investigate the combined effects of selenium on chemotherapy using docetaxel on breast cancer cell lines.MethodsUnder adherent culture conditions, two breast cancer cell lines, MDA-MB-231 and MCF-7, were treated with docetaxel at 500pM and selenium at 100nM, 1µM, or 10µM. Changes in cell growth, cell cycle duration, and degree of apoptosis after 72 hours in each treated group were evaluated.ResultsIn the MDA-MB-231 cells, the combination therapy group (docetaxel at 500pM plus selenium at 10µM) showed a significantly decreased percentage of cell growth (15% vs. 28%; P = 0.004), a significantly increased percentage of late apoptosis (63% vs. 26%; P = 0.001), and an increased cell cycle arrest in the G2/M phase (P = 0.001) compared with the solitary docetaxel therapy group. Isobologram analysis demonstrated the synergistic effect of the combination therapy in the MDA-MB-231 cells. However, in the MCF-7 cells, no significant differences in the percentage of cell growth apoptosis, the percentage of apoptosis, and the pattern of cell cycle arrest were noted between the combination therapy groups and the solitary docetaxel therapy group.ConclusionOur in vitro study indicated that the combination of selenium with docetaxel inhibits cell proliferation through apoptosis and cell arrest in the G2/M phase in MDA-MB-231 breast cancer cells.

Latin American consensus on the use of transcranial Doppler in the diagnosis of brain death.

Transcranial Doppler evaluates cerebral hemodynamics in patients with brain injury and is a useful technical tool in diagnosing cerebral circulatory arrest, usually present in the brain-dead patient. This Latin American Consensus was formed by a group of 26 physicians experienced in the use of transcranial Doppler in the context of brain death. The purpose of this agreement was to make recommendations regarding the indications, technique, and interpretation of the study of transcranial ultrasonography in patients with a clinical diagnosis of brain death or in the patient whose clinical diagnosis presents difficulties; a working group was formed to enable further knowledge and to strengthen ties between Latin American physicians working on the same topic.A review of the literature, concepts, and experiences were exchanged in two meetings and via the Internet. Questions about pathophysiology, equipment, techniques, findings, common problems, and the interpretation of transcranial Doppler in the context of brain death were answered. The basic consensus statements are the following: cerebral circulatory arrest is the final stage in the evolution of progressive intracranial hypertension, which is visualized with transcranial Doppler as a "pattern of cerebral circulatory arrest". The following are accepted as the standard of cerebral circulatory arrest: reverberant pattern, systolic spikes, and absence of previously demonstrated flow. Ultrasonography should be used - in acceptable hemodynamic conditions - in the anterior circulation bilaterally (middle cerebral artery) and in the posterior (basilar artery) territory. If no ultrasonographic images are found in any or all of these vessels, their proximal arteries are acceptable to be studied to look for a a pattern of cerebral circulatory arrest.

Curcumin cytotoxicity is enhanced by PTEN disruption in colorectal cancer cells

To investigate the effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deficiency on the cytotoxicity of chemotherapeutic agents toward colorectal cancer cells. PTEN-deficient colorectal cancer (CRC) cells were generated by human somatic cell gene targeting using the adeno-associated virus system. The cytotoxic effects of compounds including curcumin, 5-fluorouracil (5-FU), dihydroartemisinin (DHA), irinotecan (CPT-11) and oxaliplatin (OXA) on cancer cells were determined using the MTT assay. Enhanced cytotoxicity of curcumin in PTEN-deficient CRC cells was observed, and this was confirmed using clonogenic assays. Apoptosis and cell cycle progression were analyzed by flow cytometry. Levels of apoptosis and cell cycle-related proteins were examined by Western blotting. We developed an isogenic set of CRC cell lines that differed only in their PTEN status. Using this set of cell lines, we found that disruption of the PTEN gene had no effect on the sensitivity of CRC cells to 5-FU, CPT-11, DHA, or OXA, whereas PTEN disruption increased the sensitivity of CRC cells to curcumin. Loss of PTEN did not alter the curcumin-induced apoptosis in CRC cells. However, PTEN deficiency led to an altered pattern of curcumin-mediated cell cycle arrest. In HCT116 PTEN (+/+) cells, curcumin caused a G2/M phase arrest, whereas it caused a G0/G1 phase arrest in HCT116 PTEN (-/-) cells. Levels of cell cycle-related proteins were consistent with these respective patterns of cell cycle arrest. Curcumin shows enhanced cytotoxicity toward PTEN-deficient cancer cells, suggesting that it might be a potential chemotherapeutic agent for cancers harboring PTEN mutations.

Inhibition of Ion Channels and Heart Beat in Drosophila by Selective COX-2 Inhibitor SC-791

Recent findings suggest that modulation of ion channels might be implicated in some of the clinical effects of coxibs, selective inhibitors of cyclooxygenase-2 (COX-2). Celecoxib and its inactive analog 2,5-dimethyl-celecoxib, but not rofecoxib, can suppress or augment ionic currents and alter functioning of neurons and myocytes. To better understand these unexpected effects, we have recently investigated the mechanism of inhibition of human Kv2.1 channels by a highly selective COX-2 inhibitor SC-791. In this study we have further explored the SC-791 action on ion channels and heartbeat in Drosophila, which lacks cyclooxygenases and thus can serve as a convenient model to study COX-2-independent mechanisms of coxibs. Using intracellular recordings in combination with a pharmacological approach and utilizing available Drosophila mutants, we found that SC-791 inhibited voltage-activated K+ and L-type Ca2+ channels in larval body-wall muscles and reduced heart rate in a concentration-dependent manner. Unlike celecoxib and several other K+ channel blockers, SC-791 did not induce arrhythmia. Instead, application of SC-791 resulted in a dramatic slowing of contractions and, at higher concentrations, in progressively weaker contractions with gradual cessation of heartbeat. Isradipine, a selective blocker of L-type Ca2+ channels, showed a similar pattern of heart arrest, though no prolongation of contractions was observed. Ryanodine was the only channel modulating compound of those tested additionally that was capable of slowing contractions. Like SC-791, ryanodine reduced heart rate without arrhythmia. However, it could not stop heartbeat completely even at 500 µM, the highest concentration used. The magnitude of heart rate reduction, when SC-791 and ryanodine were applied together, was smaller than expected for independent mechanisms, raising the possibility that SC-791 might be interfering with excitation-contraction coupling in Drosophila heart.

Apoptotic Effects of Genistein, Biochanin-A and Apigenin on LNCaP and PC-3 Cells by p21 through Transcriptional Inhibition of Polo-like Kinase-1

Natural isoflavones and flavones are important dietary factors for prostate cancer prevention. We investigated the molecular mechanism of these compounds (genistein, biochanin-A and apigenin) in PC-3 (hormone-independent/p53 mutant type) and LNCaP (hormone-dependent/p53 wild type) prostate cancer cells. A cell growth rate and apoptotic activities were analyzed in different concentrations and exposure time to evaluate the antitumor activities of genistein, biochanin-A and apigenin. The real time PCR and Western blot analysis were performed to investigate whether the molecular mechanism of these compounds are involving the p21 and PLK-1 pathway. Apoptosis of prostate cancer cells was associated with p21 up-regulation and PLK-1 suppression. Exposure of genistein, biochanin-A and apigenin on LNCaP and PC-3 prostate cancer cells resulted in same pattern of cell cycle arrest and apoptosis. The inhibition effect for cell proliferation was slightly greater in LNCaP than PC-3 cells. In conclusion, flavonoids treatment induces up-regulation of p21 expression, and p21 inhibits transcription of PLK-1, which promotes apoptosis of cancer cells.

5‐Fluorouracil and its active metabolite FdUMP cause DNA damage in human SW620 colon adenocarcinoma cell line

5-Fluorouracil (5-FU) is an antineoplasic drug widely used to treat cancer. Its cytotoxic effect has been principally ascribed to the misincorporation of fluoronucleotides into DNA and RNA during their synthesis, and the inhibition of thymidylate synthase (TS) by FdUMP (one of the 5-FU active metabolites), which leads to nucleotide pool imbalance. In the present study, we compared the ability of 5-FU and FdUMP to induce apoptosis and to influence the cell cycle progression in human colon SW620 adenocarcinoma cells in regards to their genotoxic and clastogenic activities. Our study demonstrates that 5-FU induces SSB, DSB and apoptosis earlier than FdUMP. Interestingly, while both drugs are able to induce apoptosis, their effect on the cell cycle progression differed. Indeed, 5-FU induces an arrest in G1/S while FdUMP causes an arrest in G2/M. Independently of the temporal difference in strand breaks and apoptosis induction, as well as the differential cell cycle modulation, both drugs presented similar clastogenic effects. The different pattern of cell cycle arrest suggests that the two drugs induce different types of primary DNA lesions that could lead to the activation of different checkpoints and recruit different DNA repair pathways.

Expression pattern of zygote arrest 1 (ZAR1), maternal antigen that embryo requires (MATER), growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes in ovine oocytes and in vitro-produced preimplantation embryos

The expression patterns of four maternal effect genes (MEG), namely zygote arrest 1 (ZAR1), maternal antigen that embryo requires (MATER), growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), were determined in ovine oocytes and in vitro-produced preimplantation embryos. The existence of ZAR1 and MATER in ovine species has not been reported previously. Reverse transcription-polymerase chain reaction was performed on germinal vesicle and IVM MII oocytes, as well as in in vitro fertilised and cultured two-, four-, eight- and 12/16-cell embryos, morulae and blastocysts. Quantification of gene expression by real-time polymerase chain reaction showed the highest abundance of all transcripts analysed in the immature oocyte. During the following stages of preimplantation development, the mRNAs examined exhibited different patterns of expression, but often significant decreases were observed during maturation and maternal-embryonic transition. The transcription of the four genes did not resume with activation of the genome.

Activity of CDK1/2 Inhibitor LCQ195 Against Multiple Myeloma Cells.

Context: Conceptually, targeting proteins involved in cell cycle regulation is an appealing therapeutic strategy for multiple myeloma (MM), given the increased proliferative rate of biologically aggressive multi-drug resistant MM cells compared to not only their normal plasma cell counterparts, but also MM cells from earlier stages of the disease. Within the intricate network of signaling cascades and regulatory checkpoints involved in cell cycle progression and survival of neoplastic cells, cyclin-dependent kinases (CDKs) have emerged as intriguing therapeutic targets. We report the results of preclinical studies on the anti-MM activity of the selective CDK1/2 small molecule inhibitor NVP-LCQ195/AT9311 (Novartis Pharma/Astex Therapeutics).Methods/Results: In MTT colorimetric survival assays against a panel of 28 human MM cell lines, NVP-LCQ195 exhibited dose-dependent anti-MM activity, with IC50 values at or below ~0.5 μM (a pharmacologically relevant concentration) for 12 of 28 cell lines many of which are resistant to conventional or novel anti-MM therapies (e.g. dexamethasone, melphalan, thalidomide derivatives). NVP-LCQ195 was also active against primary MM cells isolated from heavily-pretreated/drug-resistant cases of MM. In marked contrast, the IC50 values of NVP-LCQ195 against non-malignant cells such as bone marrow stromal cells (BMSCs) and immortalized hepatocyte cells was >4 μM. In addition, both PHA-stimulated and unstimulated normal donor PBMCs were less sensitive than the majority of MM cell lines of our panel. Treatment with NVP-LCQ195 was able to overcome the protective effects conferred on MM cells by exogenous IL-6 (10ng/mL) or IGF-1 (50ng/mL), as well as by co-culture of MM cells with bone marrow stromal cells (BMSCs). NVP-LCQ195 was observed to trigger a distinct pattern of S-phase arrest, followed by eventual induction of apoptotic cell death. Mechanistic studies revealed that hsp90, B-raf, cyclin D1, and cyclin E2 levels decrease in response to NVP-LCQ195 treatment, while caspases- 3, -8 and PARP are cleaved within 16 and 24 hrs of drug treatment. We evaluated a series of combinations of this agent with conventional (e.g. dexamethasone, doxorubicin) and novel (e.g. bortezomib) anti-MM agents. No evidence of antagonism with any of these anti-MM agents was observed, indicating that combinations of NVP-LCQ195 with the aforementioned anti-MM agents can be feasible in clinical settings.Conclusion: Functional inhibition of proteins involved in cell cycle regulation remains an attractive approach for the treatment of MM. Treatment of MM cells with the CDK1/2 inhibitor NVP-LCQ195 induces, in a subset of MM cell lines, a distinct pattern of initial cell cycle arrest, anti-proliferative/pro-apoptotic molecular sequleae and eventual induction of cell death. Our results determine intriguing potential combination regimens for MM treatment. Further in vitro and in vivo studies are attempting to delineate molecular markers of MM cell responsiveness vs. resistance to NVP-LCQ195 and provide a framework for individualized treatment of select MM patients with this interesting class of compounds.

An observational study describing the geographic-time distribution of cardiac arrests in Singapore: What is the utility of geographic information systems for planning public access defibrillation? (PADS Phase I)

Public access defibrillation (PAD) has shown potential to increase cardiac arrest survival rates. To describe the geographic epidemiology of prehospital cardiac arrest in Singapore using geographic information systems (GIS) technology and assess the potential for deployment of a PAD program. We conducted an observational prospective study looking at the geographic location of pre-hospital cardiac arrests in Singapore. Included were all patients with out-of-hospital cardiac arrest (OHCA) presented to emergency departments. Patient characteristics, cardiac arrest circumstances, emergency medical service (EMS) response and outcomes were recorded according to the Utstein style. Location of cardiac arrests was spot-mapped using GIS. From 1 October 2001 to 14 October 2004, 2428 patients were enrolled into the study. Mean age for arrests was 60.6 years with 68.0% male. 67.8% of arrests occurred in residences, with 54.5% bystander witnessed and another 10.5% EMS witnessed. Mean EMS response time was 9.6 min with 21.7% receiving prehospital defibrillation. Cardiac arrest occurrence was highest in the suburban town centers in the Eastern and Southern part of the country. We also identified communities with the highest arrest rates. About twice as many arrests occurred during the day (07:00-18:59 h) compared to night (19:00-06:59 h). The categories with the highest frequencies of occurrence included residential areas, in vehicles, healthcare facilities, along roads, shopping areas and offices/industrial areas. We found a definite geographical distribution pattern of cardiac arrest. This study demonstrates the utility of GIS with a national cardiac arrest database and has implications for implementing a PAD program, targeted CPR training, AED placement and ambulance deployment.

Arrest and detention in international travellers

Systematic published reviews of national arrests of travellers abroad are rare. The pattern of arrest during international travel has implications for travellers and those involved in providing traveller services. There are also consequences for travellers who are arrested and detained abroad. The Consular Affairs Bureau, Foreign Affairs Canada assists Canadian civilians who are abroad. Beginning in 1995 the Consular Management and Operations System was used to track notifications of Canadian arrests abroad. This database was designed for the demographics, destinations, and reported causes of Canadians arrested abroad for 1996-2004. In this period, there were 6514 notifications of arrested Canadians abroad; 1024 (16%) females and 5490 (84%) males with an average age of 33.3 and 36.4 years, respectively. Recorded reasons for arrest were for females: drugs: 420 (41% of females arrested), violence: 75 (7%), other criminal acts: 198 (19%), immigration: 169 (17%), other minor causes: 20 (2%); and for males: drugs: 1554 (28% of males arrested), violence: 581 (11%), other criminal acts: 1468 (27%), immigration: 1056 (20%), other minor causes: 105 (1.9%); or the cause was not recorded for 142 women and 747 men. The USA was the most common host country for arrested Canadians. Alleged drug offences, other criminal activities, and immigration reasons were the most common cited reasons for arrest. Country of arrest reflected the pattern of Canadian international travel for recreation, business, and ancestral linkages. There are a wide-range of potential physical and mental health outcomes to arrest and imprisonment abroad that may be different in foreign jurisdictions due to language, culture, judicial processes and penalties imposed. The prison environment may also pose significant health risks.