Elucidating the clinical and genetic spectrum of inositol polyphosphate phosphatase INPP4A-related neurodevelopmental disorder.

PURPOSE: Biallelic INPP4A variants have recently been associated with severe neurodevelopmental disease in single case reports. Here, we expand and elucidate the clinical-genetic spectrum and provide a pathomechanistic explanation for genotype-phenotype correlations. METHODS: Clinical and genomic investigations of 30 individuals were undertaken alongside molecular and in silico modelling and translation reinitiation studies. RESULTS: We characterize a clinically variable disorder with cardinal features including global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures and cortical visual impairment. Our studies identify the likely pathomechanism of this genotype-phenotype correlation entailing translational reinitiation in exon 4 resulting in an N-terminal truncated INPP4A protein retaining partial functionality, associated with less severe disease. We also identified identical reinitiation site conservation in Inpp4a-/- mouse models displaying similar genotype-phenotype correlation. Additionally, we show fibroblasts from a single affected individual exhibit disrupted endocytic trafficking pathways, indicating the potential biological basis of the condition. CONCLUSION: Our studies comprehensively characterise INPP4A-related neurodevelopmental disorder and suggest genotype-specific clinical assessment guidelines. We propose the potential mechanistic basis of observed genotype-phenotype correlations entails exon 4 translation reinitiation.

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Using exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17 ± 12.4 years, range 0.1-45). Follow-up and hitherto unreported clinical features were obtained from the published 12 families. Brain MRI scans from 34 cases were reviewed. MED27-related disease manifests as a broad phenotypic continuum ranging from developmental and epileptic-dyskinetic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. It is characterized by mild to profound global developmental delay/intellectual disability (100%), bilateral cataracts (89%), infantile hypotonia (74%), microcephaly (62%), gait ataxia (63%), dystonia (61%), variably combined with epilepsy (50%), limb spasticity (51%), facial dysmorphism (38%) and death before reaching adulthood (16%). Brain MRI revealed cerebellar atrophy (100%), white matter volume loss (76.4%), pontine hypoplasia (47.2%) and basal ganglia atrophy with signal alterations (44.4%). Previously unreported 39 affected individuals had seven homozygous pathogenic missense MED27 variants, five of which were recurrent. An emerging genotype-phenotype correlation was observed. This study provides a comprehensive clinical-radiological description of MED27-related disease, establishes genotype-phenotype and clinical-radiological correlations and suggests a differential diagnosis with syndromes of cerebello-lental neurodegeneration and other subtypes of 'neuro-MEDopathies'.

Knowledge, attitudes, and practices of anaesthesia personnel towards needle stick injuries in a tertiary care hospital.

The cross-sectional, prospective study was conducted at the Aga Khan University Hospital, Karachi. A questionnaire was distributed amongst anaesthesia personnel, including faculty, residents, medical officers, technicians, recovery room nurses and pain nurses working in the Department of Anaesthesiology for >3 months. Knowledge, attitudes and practices were assessed according to the operational definitions. Of the 162 respondents, 106(65.4%) were males and 56(34.6%) were females. The overall mean age was 31±6.2 years. Adequate knowledge was found in 41(25%) subjects. Overall, 56(35%) respondents reported having had a needle-stick injury, and, among them, 49(87.5%) had a positive attitude. Also, 156(96.3%) participants followed good practices. Although entirely preventable, needle stick injuries were found to be common, indicating the need for proper implementation or revision of existing policies and attainment of safe needle devices.

Comparison of perioperative analgesia between intravenous paracetamol and fentanyl for rigid hysteroscopy: A randomised control trial.

OBJECTIVE: To compare efficacy of intravenous paracetamol and fentanyl for intra-operative and post-operative analgesia in patients undergoing rigid hysteroscopy. METHOD: The prospective randomised control trial was conducted at Aga Khan University Hospital, Karachi, from October 2016 to June 2017, and comprised patients aged 18-65 years with American Society of Anesthesiologists grade I or II undergoing hysteroscopy who were randomised into paracetamol group P and fentanyl group F. Anaesthesia induction technique was standardised and analgesia in group P was paracetamol 15mg/Kg administered 15-30 minutes pre-surgery, and in group F, it was fentanyl 2mcg/kg administered at induction of anaesthesia. Intra-operative pain was assessed by changes in heart rate, systolic, diastolic and mean arterial blood pressure, and post-operative pain was assessed using the visual analogue scale. Data was analysed using SPSS 19. RESULTS: Of the 60 patients, there were 30(50%) in each of the two groups. Baseline parameters were similar in the groups except for age differences (p<0.011). In group P, mean systolic blood pressure at 10,15, 20, 25 and 30 minutes, mean diastolic blood pressure at 20, 25 minutes, and mean arterial blood pressure at 20 minutes were statistically significant (p<0.05) compared to group F. The mean heart rate was not significant between the groups (p>0.05). Post-operative pain scores were similar at 0, 15 and 30 minutes (p>0.05). Rescue analgesia was needed in 3(10%) patients in each group on arrival in the recovery room. CONCLUSIONS: Intravenous paracetamol offered analgesic efficacy similar to fentanyl for rigid hysteroscopy in ambulatory surgery.

Quality assurance audit in adult cardiac anaesthesia.

OBJECTIVE: To assess different anaesthesia-related quality indicators during adult cardiac surgery. METHODS: The prospective clinical audit was conducted at the Aga Khan University Hospital, Karachi, from October 2016 to March 2017, and comprised all adult patients scheduled for cardiac surgery. Different anaesthesia-related quality indicators were observed during the pre-induction phase, before the cardiopulmonary bypass, during the procedure, and post-surgery till the transfer from the operating room to the cardiac intensive care unit. Data was analysed using SPSS 19. RESULTS: Of the 264 patients, 217(82.2%) had complete record; 160(73.7%) males and 57(26.3%) females. The overall mean age was 56.56±12.46 years. In the pre-induction phase, difficult intravenous and invasive line access was seen in 42(19.3%) patients. Inappropriate information in the preoperative form was found in 6(2.8%) patients, and preoperative drugs for anxiolysis were used in 145(66.8%) patients. Haemodynamic issues were significant during the surgery in 15(6.9%) patients. In the post-surgery period, abnormal activated clotting time was found in 17(7.8%) patients, while monitoring problems were faced in 7(3.2%) cases during transfer to cardiac intensive care unit. CONCLUSIONS: It will help to develop quality improvement policies to enhance patient safety, satisfaction and better outcome.

Two Novel and Five Rare Mutations in the Non Coding Regions of the ß-Globin Gene in the Iranian Population.

ß-Thalassemia (ß-thal) is one of the most frequent genetic disorder in Iran with great mutational diversity. In this study, we describe two novel and five rare mutations in the non coding regions of the ß-globin gene; these mutations were identified in the non coding regions of the ß-globin gene (HBB) in the heterozygous state. Three alterations were detected in the promoter region, including -9 (C>G) [HBB: c.59C>G (novel mutation)], -54 (G>A) (HBB: c.-104G>A) and -57 (A>T) (HBB: c.-107A>T), three changes in the 5' untranslated region (5'UTR) including +11 (C>G) [HBB: c.-40C>G (novel mutation)], +41 (A>T) (HBB: c.-10A>T) and +43 (C>G) (HBB: c.-8C>G) and one mutation in the 3'UTR 62 (A>G) (HBB: c.*62A>G). Five mutations including -54, -57, +41, +11 and +43 were predicted to be deleterious in all except one in silico prediction tool, and the remaining two mutations were found to be most likely polymorphisms. In conclusion, two novel mutations were reported for the first time worldwide and five rare changes have not been reported previously in any other part of Iran. In the absence of further data, it is not possible to consider them as mutations that determine an ascertained healthy carrier state.

Response of Pseudokirchneriella subcapitata in Free and Alginate Immobilized Cells to Heavy Metals Toxicity.

Effects of 12 heavy metals on growth of free and alginate-immobilized cells of the alga Pseudokirchneriella subcapitata were investigated. The tested metals ions include Al, As, Cd, Co, Cr, Cu, Hg, Se, Ni, Pb, Sr, and Zn. Toxicity values (EC50) were calculated by graphical interpolation from dose-response curves. The highest to the lowest toxic metals are in the order Cd > Co > Hg > Cu > Ni > Zn > Cr > Al > Se > As > Pb > Sr. The lowest metal concentration (mg L-1) inhibiting 50% (EC50) of algal growth of free and immobilized (values in parentheses) algal cells were, 0.018 (0.09) for Cd, 0.03 (0.06) for Co, 0.039 (0.06) for Hg, 0.048 (0.050) for Cu, 0.055 (0.3) for Ni, 0.08 (0.1) for Zn, 0.2 (0.3) for Cr, 0.75 (1.8) for Al, 1.2 (1.4) for Se, 3.0 (4.0) for As, 3.3 (5.0) for Pb, and 160 (180) for Sr. Free and immobilized cultures showed similar responses to Cu and Se. The free cells were more sensitive than the immobilized ones. Accordingly, the toxicity (EC50) of heavy metals derived only form immobilized algal cells might by questionable. The study suggests that batteries of alginate-immobilized algae can efficiently replace free algae for the bio-removal of heavy metals.

Genome-wide single nucleotide polymorphism-based autozygosity mapping facilitates identification of mutations in consanguineous families with epidermolysis bullosa.

Autozygosity mapping (AM) is a technique utilised for mapping homozygous autosomal recessive (AR) traits and facilitation of genetic diagnosis. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using both short tandem repeat (STR) and genome-wide single nucleotide polymorphism (SNP) array-based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analysed with an EB-targeted next-generation sequencing (NGS) panel. NGS identified mutations in five additional cases, initially undiagnosed due to the presence of compound heterozygosity, deep intronic mutations or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 of 46 cases (95.7%) diagnosed genetically.

Electrochemical Pseudocapacitors Based on Ternary Nanocomposite of Conductive Polymer/Graphene/Metal Oxide: An Introduction and Review to it in Recent Studies.

This review gives an overview of the synthesis, surface and electrochemical investigations over ternary nanocomposite of conductive polymers in the development of new supercapacitors. They utilize both Faradaic and non-Faradaic procedures to store charge, leading to higher specific capacitance and energy density, higher cell voltage, longer life cycle and moderated power density. Owing to a unique combination of features such as superb electrical conductivity, corrosion resistance in aqueous electrolytes, highly modifiable nanostructures, long cycle life and the large theoretical specific-surface area, the use of ternary nanocomposites as a supercapacitor electrode material has become the focus of a significant amount of current scientific researches in the field of energy storage devices. In these nanocomposites, graphene not only can be utilized to provide a substrate for growing nanostructured polymers in a polymer-carbon nanocomposite structure in order to overcome the insulating nature of conductive polymers at dedoped states, but also is capable of providing a platform for the decoration of metal oxide nanoparticles to avoid their agglomeration. In this regard, synthesis, characterization and performance of different ternary nanocomposites of conductive polymer/graphene/metal oxide are discussed in detail. These remarkable results demonstrate the exciting commercial potential for high performance, environmentally friendly and low-cost electrical energy storage devices based on ternary nanocomposite of conductive polymer/graphene/metal oxide.

Multicenter International Survey on the Clinical Practice of Ultra-Fast-Track Anesthesia with On-Table Extubation in Pediatric Congenital Cardiac Surgery.

OBJECTIVE: To describe global practices for on-table extubation (OTE) in pediatric cardiac anesthesia in European and non-European countries. DESIGN: Multiple-choice, web-based survey with 34 questions addressing organizational data, existence of OTE programs, inclusion and exclusion criteria for OTE, and intraoperative and immediate postoperative management. SETTING: Online survey endorsed by the European Association of Cardiothoracic Anesthesiologists. PARTICIPANTS: Anesthesiologists departments in European and non-European pediatric cardiac surgical centers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The survey was sent to 144 pediatric cardiac surgical centers in 29 countries as a web-based questionnaire. Addressees were pediatric cardiac anesthesiologists who were members of European Association of Cardiothoracic Anesthesiologists or were known to the authors. The response rate was 63%. Fifty percent of the respondents were practicing in university hospitals. The survey demonstrated that 76% of the respondents practiced OTE, with 50% of the pediatric cardiac anesthesiologists regularly performing OTE in different proportions, ranging from 1 to 51% of on-pump pediatric cardiac surgeries. Seventy-seven percent of respondents made their decision to perform OTE on an individual case-by-case basis. Seventy-eight percent of the congenital cardiac lesions deemed eligible for OTE fell into Risk Adjustment for Congenital Heart Surgery-1 categories 1 and 2. In patients for whom OTE was planned, anesthesia primarily was maintained using a combined inhalational and intravenous technique. The main reasons not to perform OTE were that it was deemed to provide no major advantage (45%), to be dangerous (9%), or to decrease operating room efficiency by increasing operating room turnover time (36%). CONCLUSION: The survey demonstrated that the majority of the approached pediatric cardiac anesthesiologists practice OTE regularly in pediatric cardiac surgery. Frequency of OTE and inclusion criteria vary widely. The observations made in this survey should prompt appropriately powered, randomized controlled clinical trials to examine the effect of OTE on various effectiveness and safety outcomes.

Isoflurane alone versus small dose propofol with isoflurane for removal of laryngeal mask airway in children-a randomized controlled trial.

OBJECTIVE: To compare the safety of laryngeal mask airway removal using two different deep anaesthesia techniques in paediatric patients. METHODS: The Randomized Control Trial was conducted at Aga Khan University Hospital, Karachi, from April 2012 to November 2013, and comprised patients aged 2-10 years scheduled for infraumbilical surgeries. Anaesthesia was induced with sevoflurane and later it was maintained by is oflurane, oxygen and nitrous oxide. The laryngeal mask airway was removed in the intervention group-I at 0.4 minimum alveolar concentration of isoflurane with propofol 1mg/kg. In the control group-II, it was removed at 1.2 minimum alveolar concentration of isoflurane alone. SPSS 19 was used for data analysis. RESULTS: Of the 50 patients, there were 25(50%) in each of the two groups. Overall, there were 46(92%) males and 4(8%) females. Incidence of airway obstruction and teeth clenching was significantly higher in group-II (p<0.05 each). Emergence duration was also significantly increased in group-II compared to group-I (p=0.001). The Post-Anaesthesia Care Unit stay timing was not significantly different between the groups (p=0.74). CONCLUSIONS: Laryngeal mask airway removal under deep anaesthetic technique of low-dose propofol with isoflurane was found to be associated with minimal adverse airway events than isoflurane alone in paediatric patients.

Mutation Screening of the Krüppel-like Factor 1 Gene in Individuals With Increased Fetal Hemoglobin Referred for Hemoglobinopathy Investigation in South of Iran.

BACKGROUND: Any mutation in the Krüppel-like factor 1 (KLF1) gene may interfere with its proper related function in the erythropoiesis process and lead to alterations in proper activation of its downstream protein through globin switching, which results in an increase in fetal hemoglobin (HbF). This study aimed to investigate whether KLF1 mutation can associate with high level of HbF in individuals with increased fetal hemoglobin referred for screening of hemoglobinopathies in south of Iran. MATERIALS AND METHODS: The human KLF1 gene was amplified via the polymerase chain reaction procedure, and sequencing was used to determine any mutation in these patients. Moreover, XmnI polymorphisms in the position of -158 of γ-globin gene promoter were analyzed in all patients by polymerase chain reaction restriction fragment length polymorphism. RESULT: Analysis of sequencing revealed a missense mutation in the KLF1 gene, p.Ser102Pro (c.304T>C), which was detectable in 10 of 23 cases with elevated HbF level. This mutation was only detected in individuals who had a HbF level between 3.1% and 25.6%. Statistical analysis showed that the frequency of C allele is significantly correlated with a high level of HbF (P<0.05). The allele frequency of positive result of XmnI polymorphism in individuals with increased HbF level was also significant, which showed an association with increased HbF level (P<0.05). CONCLUSIONS: To the best of our knowledge, this is the first report of p.Ser102Pro (c.304T>C) in the KLF1 gene in ß-thalassemia patients with increased level of fetal hemoglobin. According to statistical results of p.Ser102Pro mutation and XmnI polymorphism, it has been strongly suggested that both polymorphisms have an association with increased HbF samples. These nucleotide changes alone may not be the only elements raising the level of HbF, and other regulatory and modifying factors also play a role in HbF production.

Annual Southeast Asia haze increases respiratory admissions: A 2-year large single institution experience.

BACKGROUND AND OBJECTIVE: The Southeast Asia (SEA) haze is an annual problem and at its worst could produce respirable particles of concentrations up to 500 µg/m3 which is five times the level considered as 'unhealthy'. However, there are limited reports examining the direct clinical impact of the annual haze. This study examines the effects of the SEA haze on respiratory admissions. METHODS: Data from all respiratory admissions in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from 1st January 2014 to 31st December 2015 were collected retrospectively from chart and electronic database. A total of 16 weeks of haze period had been formally dated by the Department of Environment using the definition of weather phenomenon leading to atmospheric visibility of less than 10 km. Multivariable regression analyses were performed to estimate rate ratios and 95% CI. RESULTS: There were 1968 subjects admitted for respiratory admissions in UKMMC during the study period. Incidence rates per week were significantly different between the two groups with 27.6 ± 9.2 cases per week during the haze versus 15.7 ± 6.7 cases per week during the non-haze period (P < 0.01). A total of 4% versus 2% was admitted to the intensive care unit in the haze and the non-haze groups, respectively (P = 0.02). The mean ± SD lengths of stay was 12.1 ± 5.2 days; the haze group had a longer stay (18.2 ± 9.7 days) compared to the non-haze groups (9.7 ± 3.9) (P < 0.001). CONCLUSION: The annual SEA haze is associated with increased respiratory admissions.

Incidence and pattern of Thrombocytopenia in cardiac surgery patients.

OBJECTIVE: To observe the incidence and pattern of thrombocytopenia in cardiac surgery patients. METHODS: This prospective, cohort study was conducted at the Aga Khan University Hospital, Karachi, from November 2014 to April 2015, and comprised adult cardiac patients. Patients with platelet count less than 150,000 x 109/L, history of malignancy, immune thrombocytopenic purpura and on chemo or radiotherapy were excluded. All information including demographics, platelet count, heparin doses, total cardiopulmonary bypass time, cross-clamp time, blood products transfused, any thromboembolic complication and the presence of infection were recorded on a pre-designed proforma. SPSS 19 was used for data analysis.. RESULTS: Of the 177 patients, 130(73.4%) were males and 47(26.6%) were females. The overall mean age was 59.21±10.99 years. Thrombocytopenia was observed in 167(94.4%) patients. Of them, platelet count dropped below 50% in 71(42.5%) patients, 30-50% in 68(40.7%) patients and 20-30% in 28(16.8%) from the baseline value. Regarding pattern of thrombocytopenia, maximum drop in platelet count was noticed on 2nd and 3rd day of surgery. Furthermore, 9(5.3%) patients developed severe thrombocytopenia (<50,000 x 109/L). CONCLUSIONS: The incidence of thrombocytopenia and its severity after cardiac surgery was very high in our study population when compared with western population.

Effect of steroids on inflammatory markers and clinical parameters in congenital open heart surgery: a randomised controlled trial.

BACKGROUND: Cardiopulmonary bypass is associated with systemic inflammatory response. Steroids suppress this response, although the therapeutic evidence remains controversial. We hypothesised that intravenous steroids in children undergoing open-heart surgery would decrease inflammation leading to better early post-operative outcomes. We conducted a randomised controlled trial to evaluate the trends in the levels of immunomodulators and their effects on clinical parameters. OBJECTIVE: To assess the effects of intravenous steroids on early post-operative inflammatory markers and clinical parameters in children undergoing open-heart surgery. MATERIALS AND METHODS: A randomised controlled trial involving 152 patients, from one month up to 18 years of age, who underwent open-heart surgery for congenital heart disease from April 2010-2012 was carried out. Patients were randomised and administered either three scheduled intravenous pulse doses of dexamethasone (1 mg/kg) or placebo. Blood samples were drawn at four time intervals and serum levels of inflammatory cytokines - Interleukin-6, 8, 10, 18, and tumour necrosis factor-alpha - were measured. Clinical parameters were also assessed. RESULTS: Blood cytokine levels were compared between the dexamethasone (n=65) and placebo (n=64) groups. Interleukin-6 levels were lower at 6 and 24 hours post-operatively (p<0.001), and Interleukin-10 levels were higher 6 hours post-operatively (p<0.001) in the steroid group. Interleukin-8, 18, and tumour necrosis factor-alpha levels did not differ between the groups at any time intervals. The clinical parameters were similar in both the groups. CONCLUSION: Dexamethasone caused quantitative suppression of Interleukin-6 and increased Interleukin-10 activation, contributing to reduced immunopathology, but it did not translate into clinical benefit in the short term.

Intraoperative ventilatory management of adult tracheoesophageal fistula.

Iatrogenic Tracheo Esophageal Fistula (TEF) in adults is a rare complication occurring secondary to trauma and prolonged intubation. There is very scarce data regarding its airway management and that too is from the paediatric age group. We describe the case of a young male undergoing TEF repair. We started with routine tracheal intubation but during surgery our tracheal tube was hindering surgical repair. So we used intermittent ventilation by passing the tracheal tube distal to the fistula and then pulling it back and providing clear surgical field during apnoea. It was done several times until the repair was completed successfully. Different airway management techniques are described in literature with the most common being oral intubation and placement of cuff distal to the fistula. However it may need to be modified according to the situation. We used a different technique for ventilation and will discuss it's pros and cons.

Fast Track Extubation In Adult Patients On Pump Open Heart Surgery At A Tertiary Care Hospital.

BACKGROUND: Fast-track cardiac surgery programs have been established as the standard of cardiac surgical care. Studies have shown that early extubation in elective cardiac surgery patients, including coronary and non-coronary open-heart surgery patients does not increase perioperative morbidity and mortality. The objective of this observational study was to determine the success and failure profile of fast track extubation (FTE) practice in adult open-heart surgical patients. METHODS: The study was conducted at cardiac operating room and Cardiac Intensive Care Unit (CICU) of a tertiary care hospital for a period of nine months, i.e., from Oct 2014 to June-2015. All on pump elective adult cardiac surgery patients including isolated CABG, isolated Valve replacements, combined procedures and aortic root replacements were enrolled in the study. Standardized anesthetic technique was adopted. Surgical and bypass techniques were tailored according to the procedure. Success of Fast track extubation was defined as extubation within 6 hours of arrival in CICU. RESULTS: A total of 290 patients were recruited. The average age of the patients was 56.3±10.5 years. There were 77.6% male and 22.4% female patients. Overall success rate was 51.9% and failure rate was 48.1%. The peri-operative renal insufficiency, cross clamp time and CICU stay (hours) were significantly lower in success group. Re-intubation rate was 0.74%. CONCLUSION: The perioperative parameters were significantly better in success group and the safety was also demonstrated in the patients who were fast tracked successfully. To implement the practice in its full capacity and benefit, a fast track protocol needs to be devised to standardize the current practices and to disseminate the strategy among junior anaesthesiologists, perfusionists and nursing staff.

Efficacy of intravenous paracetamol on pressor response in patients undergoing cesarean section under general anesthesia.

BACKGROUND AND AIMS: Profound hemodynamic alterations due to stress and pain during endotracheal intubation may cause deleterious effects. The purpose of this study was to evaluate the effect of intravenous (IV) paracetamol on hemodynamic changes due to endotracheal intubation during cesarean section under general anesthesia. MATERIAL AND METHODS: Random allocation of one hundred and ten patients in two groups (Group A - placebo and Group B - paracetamol), was achieved as per computer generated table. The placebo (normal saline) and paracetamol solutions looked identical as both were available in 100 ml piggy bags and were labeled as study drug. Infusion of the drug was given 1 h before surgery. Two baseline readings of heart rate, systolic blood pressure (BP), diastolic BP and mean BP were recorded before induction, and these readings were repeated during intubation. Detrimental effect on neonate was evaluated by Apgar score measured at 1 and 5 min after birth. RESULTS: There were no significant demographic differences found between the two groups. Hemodyamic changes during intubation also did not differ between the two groups. CONCLUSION: Administration of IV paracetamol 1 h before cesarean section has no significant effect in preventing hemodynamic changes at the time of endotracheal intubation.

Incidence and clinical importance of BCR-ABL1 mutations in Iranian patients with chronic myeloid leukemia on imatinib.

Mutations of the BCR-ABL1 kinase domain seem to be the most common cause of imatinib mesylate resistance in chronic myeloid leukemia (CML). We screened BCR-ABL1 kinase domain mutations using nested reverse transcriptase polymerase chain reaction and direct sequencing in 30 CML patients including 22 resistant patients and 8 patients with optimal response to imatinib. Three mutations of two different types were identified in 3 of 22 (13.6%) resistant patients. Two patients had p.E355G mutation in the catalytic domain, and the third patient had p.G398R in the activation loop that is reported here for the first time. No mutation was found in patients with optimal response to imatinib. The frequency of mutations was similar in patients with primary resistance compared with patients with secondary resistance (25 vs 11%; P=1). Mutation status had no impact on the overall survival and progression-free survival. p.E355G mutation was correlated with shorter survival (P=0.047) in resistant patients. We conclude that BCR- ABL1 mutations are associated with the clinical resistance, but may not be considered the only cause of resistance to imatinib. Mutational analysis may identify resistant patients at risk of disease progression.

Fungi contamination of drinking water.

Aquatic fungi commonly infest various aqueous environments and play potentially crucial roles in nutrient and carbon cycling. Aquatic fungi also interact with other organisms to influence food web dynamics. In recent decades, numerous studies have been conducted to address the problem of microorganism contamination of water. The major concern has been potential effects on human health from exposure to certain bacteria, viruses, and protozoa that inhabit water and the microbial metabolites,pigments, and odors which are produced in the water, and their effects on human health and animals. Fungi are potentially important contaminants because they produce certain toxic metabolites that can cause severe health hazards to humans and animals. Despite the potential hazard posed by fungi, relatively few studies on them as contaminants have been reported for some countries.A wide variety of fungi species have been isolated from drinking water, and some of them are known to be strongly allergenic and to cause skin irritation, or immunosuppression in immunocompromised individuals (e.g., AIDS, cancer, or organ transplant patients). Mycotoxins are naturally produced as secondary metabolites by some fungi species, and exposure of humans or animals to them can cause health problems. Such exposure is likely to occur from dietary intake of either food,water or beverages made with water. However, mycotoxins, as residues in water,may be aerosolized when showering or when being sprayed for various purposes and then be subject to inhalation. Mycotoxins, or at least some of them, are regarded to be carcinogenic. There is also some concern that toxic mycotoxins or other secondary metabolites of fungi could be used by terrorists as a biochemical weapon by adding amounts of them to drinking water or non drinking water. Therefore, actions to prevent mycotoxin contaminated water from affecting either humans or animals are important and are needed. Water treatment plants may serve to partially accomplish this, by first filtering the water and finally by adding disinfection treatments adequate to remove or mitigate fungi or their toxic metabolites.