Secure Enhancement for MQTT Protocol Using Distributed Machine Learning Framework.

The Message Queuing Telemetry Transport (MQTT) protocol stands out as one of the foremost and widely recognized messaging protocols in the field. It is often used to transfer and manage data between devices and is extensively employed for applications ranging from smart homes and industrial automation to healthcare and transportation systems. However, it lacks built-in security features, thereby making it vulnerable to many types of attacks such as man-in-the-middle (MitM), buffer overflow, pre-shared key, brute force authentication, malformed data, distributed denial-of-service (DDoS) attacks, and MQTT publish flood attacks. Traditional methods for detecting MQTT attacks, such as deep neural networks (DNNs), k-nearest neighbor (KNN), linear discriminant analysis (LDA), and fuzzy logic, may exist. The increasing prevalence of device connectivity, sensor usage, and environmental scalability become the most challenging aspects that novel detection approaches need to address. This paper presents a new solution that leverages an H2O-based distributed machine learning (ML) framework to improve the security of the MQTT protocol in networks, particularly in IoT environments. The proposed approach leverages the strengths of the H2O algorithm and architecture to enable real-time monitoring and distributed detection and classification of anomalous behavior (deviations from expected activity patterns). By harnessing H2O's algorithms, the identification and timely mitigation of potential security threats are achieved. Various H2O algorithms, including random forests, generalized linear models (GLMs), gradient boosting machine (GBM), XGBoost, and the deep learning (DL) algorithm, have been assessed to determine the most reliable algorithm in terms of detection performance. This study encompasses the development of the proposed algorithm, including implementation details and evaluation results. To assess the proposed model, various evaluation metrics such as mean squared error (MSE), root-mean-square error (RMSE), mean per class error (MCE), and log loss are employed. The results obtained indicate that the H2OXGBoost algorithm outperforms other H2O models in terms of accuracy. This research contributes to the advancement of secure IoT networks and offers a practical approach to enhancing the security of MQTT communication channels through distributed detection and classification techniques.

Nuclear medicine imaging findings in end-stage renal disease and renal transplant complications.

The aim of this review is to discuss end-stage renal disease (ESRD) and renal transplant complications and present the nuclear medicine imaging findings. The conditions discussed are renal osteodystrophy, metastatic calcification, and renal transplant complications, such as vascular occlusion and acute tubular necrosis. A total of eight nuclear medicine imaging scintigraphy primarily of bone and renal scintigraphy were selected and the imaging features of the complications are discussed. This article highlights the role of nuclear medicine imaging in diagnosis, quantitative and qualitative assessment of renal function, and monitoring of complications associated with ESRD and renal transplant.

Risk Assessment of Pesticide Residues by GC-MSMS and UPLC-MSMS in Edible Vegetables.

In recent years, there has been a significant increase related to pesticide residues in foods, which may increase the risks to the consumer of these foods with the different quality and concentrations of pesticide residues. Pesticides are used for controlling pests that reduce yields. On the other hand, it has become a major public health concern due to its toxic properties. Thus, the objective of the current study employed the application of Quick Easy Cheap Effective Rugged Safe (QuEChERS) method, in combination with gas and liquid chromatography-tandem mass spectrometric detection (GCMSMS, LCMSMS) in order to determine 137 pesticide residues (63 insecticides, 41 acaricides, 40 herbicide, 55 fungicide, nematicide, growth regulator, Chitin synthesis inhibitors, and Juvenile hormone mimics), in 801 vegetables such as 139 tomatoes, 185 peppers, 217 squash, 94 eggplants, and 166 cucumbers from different locations in Hail and Riyadh cities. The results showed that the majority of pesticide residues were detected for each of the following pesticides: acetaimpride, metalaxyl, imidaclopride, bifenthrin, pyridaben, difenoconazole, and azoxystrobien, which were repeated in the samples studied 39, 21, 11, 10, 8, 7, and 5, respectively. In addition, results observed that the tomato was the most contaminated with pesticide residues; it was contaminated with 19 compounds and was followed by pepper, cucumber, and squash, and the last commodity in the contaminated ranking was eggplant. The highest calculated estimated daily intakes (EDIs) were recorded for tomatoes which were estimated between 0.013 to 0.516 mg/kg of body weight per day (bw/day) while the lowest EDIs value was between 0.000002 to 0.0005 mg/kg of bw/day for cucumber. Results indicated that the EDIs values were lower than the acceptable daily intake (ADI) values. Results observed that the most of pesticide residues exposure in food consumption in Saudi Arabia were lower than ADIs. In addition, the highest value for health risk index (HRI) was recorded with Ethion residue in tomato, but in sweet pepper, the highest value for HRI was 127.5 in the form of fipronil residue. On the other hand, results found that the highest values of HRI were 1.54, 1.61, and 0.047 for difenoconazole, bifenthrin, and pyridaben residues in squash, eggplant, and cucumber.

Characterization and Biodegradation of Phenol by Pseudomonas aeruginosa and Klebsiella variicola Strains Isolated from Sewage Sludge and Their Effect on Soybean Seeds Germination.

Phenols are very soluble in water; as a result, they can pollute a massive volume of fresh water, wastewater, groundwater, oceans, and soil, negatively affecting plant germination and animal and human health. For the detoxification and bioremediation of phenol in wastewater, phenol biodegradation using novel bacteria isolated from sewage sludge was investigated. Twenty samples from sewage sludge (SS) were collected, and bacteria in SS contents were cultured in the mineral salt agar (MSA) containing phenol (500 mg/L). Twenty colonies (S1 up to S20) were recovered from all the tested SS samples. The characteristics of three bacterial properties, 16S rDNA sequencing, similarities, GenBank accession number, and phylogenetic analysis showed that strains S3, S10, and S18 were Pseudomonas aeruginosa, Klebsiella pneumoniae, and Klebsiella variicola, respectively. P. aeruginosa, K. pneumoniae, and K. variicola were able to degrade 1000 mg/L phenol in the mineral salt medium. The bacterial strains from sewage sludge were efficient in removing 71.70 and 74.67% of phenol at 1000 mg/L within three days and could tolerate high phenol concentrations (2000 mg/L). The findings showed that P. aeruginosa, K. pneumoniae, and K. variicola could potentially treat phenolic water. All soybean and faba bean seeds were germinated after being treated with 250, 500, 750, and 1000 mg/L phenol in a mineral salt medium inoculated with these strains. The highest maximum phenol removal and detoxification rates were P. aeruginosa and K. variicola. These strains may help decompose and detoxify phenol from industrial wastewater with high phenol levels and bioremediating phenol-contaminated soils.

ACCEPTANCE AND UTILIZATION OF MODERN FAMILY PLANNING METHODS AMONG WOMEN OF CHILD BEARING AGE IN RURAL COMMUNITIES OF NORTH-EASTERN NIGERIA.

Introduction: Modern family planning is one of the most "health-promoting" and cost-effective activities in public health promotion and has the potential to avert approximately 30% of maternal and 10% of child deaths. Family planning is an important preventive measure against maternal and child morbidity and mortality. It is an essential component of primary health care and reproductive health. It confers important health and development benefits to individuals, families, communities, and the nation at large. Objectives: The study examined the acceptance and utilization of modern family planning methods among women of childbearing age in Potiskum town of Yobe State, North-eastern Nigeria. Methodology: A descriptive cross-sectional study design was adopted for the study. A semi-structured questionnaire was used to collect data from 271 respondents comprising women of childbearing age (15-49 years) residing in Bolewa 'B', Yerimaram, and DogoNini wards of Potiskum town, Yobe State. A multi-stage sampling technique was used to select the participants for the study. Results: The findings of the study revealed that the women of child-bearing age in Potiskum town, Yobe State have a high level of knowledge on modern family planning methods (88.6%) with friends and relatives as the predominant source of information (60.4%). More than half of the respondents (54.2%) have good utilization of modern family planning with cultural and religious misconceptions playing vital roles. The unmet needs were found to be (37.4%). Established determinants of utilization of modern family planning services among the respondents include male noninvolvement, side effects, religion, and distance beyond 5km to a health facility. Conclusion: In conclusion, despite a good level of knowledge of modern contraceptives among the respondents, only half utilize the services. It is recommended among others that, there is a need for the government, through the Ministry of Health, to revive and support family planning education at both household and community levels that targets the woman and her partner. This could be undertaken through community mobilization and engagement using print and mass media, traditional leaders, community resource groups, market places as well as newsletters, posters, and social media.

One-year results of stent graft repair for carotid artery pseudo-aneurysm in patients with Behcet's disease.

OBJECTIVES: Behcet's disease is a multisystem disorder of unknown etiology with vascular complications. This study reviewed the mid-term outcome of Behcet's disease patients with carotid artery pseudo-aneurysms treated by endovascular stent-graft repair at our unit. METHODS: During a period of 11 years, six cases were included. Postoperative ultrasound duplex results were recorded along with computed tomography angiography report done a year after intervention. RESULTS: The mean age (±SD) was 38 (±5.2) years. The mean (±SD) pseudo-aneurysm size was 33 (±12.2) mm. Technical success was 83%; failed cannulation of the internal carotid artery was encountered in one case. On day 2 post-operative, a duplex ultrasound revealed complete exclusion and thrombosis of the false aneurysm in all cases. A year later, a computed tomography angiography revealed a primary patency rate of 80%, and only one case had a recurrent pseudo-aneurysm at the distal margin of the stent graft. All cases, however, had complete thrombosis in the pseudo-aneurysms lumen with a mean (±SD) regression in size of 18 (±6) mm. The mean (±SD) percentage of in-stent stenosis was 34.5% (±11.73%). CONCLUSIONS: Stent graft repair for carotid artery pseudo-aneurysm in Behcet's disease patients might be the preferable first line of treatment since it had a high technical success and mid-term primary patency rates, with additional fact that it obviously avoids the hazardous complications of surgery.

Streptococcus, Centrocestus formosanus and Myxobolus tilapiae concurrent infections in farmed Nile tilapia (Oreochromis niloticus).

Stress triggered concurrent microbial/parasitic infections are prevalent in earthen pond based farmed Nile tilapia Oreochromis niloticus. In the current study, a total of thirty five O. niloticus were collected from a commercial fish farm with a history of severe mortalities at Port Said, Egypt. Nile tilapia samples were subjected to bacteriological, parasitological and pathological examinations. Twenty one Enterococcus fecalis and 15 Streptococcus agalactiae isolates were presumptively identified utilizing the semi-automated API 20 Strept test kit. The identities of the retrieved bacteria were confirmed by the sequencing of 16 S rRNA gene. Moribund O. niloticus were found to be heavily infected by one or both of Centrocestus formosanus encysted metacercariae (EMC) and/or Myxobolus tilapiae spores presenting a unique form of synergistic and/or symbiotic relationship. The identities of both parasites were confirmed through morphological and molecular characterization. Variable circulatory, degenerative, necrotic and proliferative changes were also noticed in hematopoietic organs. Interestingly, multiple myxobolus spores and EMC were noticed in some histological sections. It was obvious that the current concurrent bacterial and parasitic infections are triggered by the deleterious effects of some stressing environmental conditions. The unfavorable climatic conditions (high temperature and high relative humidity) recorded at the surge of mortalities are probable predisposing stress factors.

Cost-effectiveness of mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage: an economic evaluation based on the MifeMiso trial.

OBJECTIVE: To assess the cost-effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage. DESIGN: Within-trial economic evaluation and model-based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost-effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS). SETTING: Twenty-eight UK NHS early pregnancy units. SAMPLE: A cohort of 711 women aged 16-39 years with ultrasound evidence of a missed miscarriage. METHODS: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets. MAIN OUTCOME MEASURES: Cost per additional successfully managed miscarriage and quality-adjusted life years (QALYs). RESULTS: For the within-trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7-12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI -0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26-£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model-based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model-based evidence suggests that the intervention is a less effective but less costly strategy than surgical management. CONCLUSIONS: The within-trial analysis found that based on cost-effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage. TWEETABLE ABSTRACT: The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages.

Elemental Concentration in the Biological Samples of Pakistani Male Breast Cancer Patients.

BACKGROUND: Breast cancer is an uncommon (rare) disease in men, approximately 1% of the total breast cancer cases in the world. By reason of the rare occurrence, there is no clinical or hospital study giving the information about the essential trace and toxic elements in the biological samples of male breast cancer patients. METHODS: The aim of current study was to estimate association among essential trace {zinc (Zn), iron (Fe) and copper (Cu)} and toxic {cadmium (Cd) and lead (Pb)} elements in human biological samples particularly blood, serum, scalp hair, of male breast cancer patients (n = 14, age range 52 - 58 years) residents of Hyderabad, Pakistan. For comparative purposes, the biological samples of referent persons (n = 37) of the same age groups were also be analyzed. Microwave oven mediated digestion method was employed, and digestion of samples was carried out with the help of 2:1 mixture solution of HNO3 (65%) and H2O2 (30%). Atomic absorption spectrometry was employed for the determination of elemental concentrations from the microwave oven employed digested samples. RESULTS: The found average of essential elements (zinc, iron, and copper) in samples of male breast cancer patients was found to be lower, while cadmium and nickel were found to be higher, when compared with samples from referents (p < 0.001). CONCLUSIONS: These data will be helpful for treatment of male breast cancer patients to improve his health and life.

Preemptive Stem Cells Ameliorate Neuropathic Pain in Rats: A Central Component of Preemptive Analgesia.

The present study aims to investigate the efficacy of intravenously injected mesenchymal stem cells (MSCs) in treating neuropathic pain either before or after its induction by a chronic constriction injury (CCI) model. Rats were divided into four groups: control group, neuropathic group, and treated groups (pre and postinduction) with i.v. mononuclear cells (106 cell/mL). For these rats, experimental testing for both thermal and mechanical hyperalgesia was evaluated. The cerebral cortex of the rats was dissected, and immunohistochemical analysis using anti-proliferating cell nuclear antigen (PCNA), CD117, nestin, and glial fibrillary acidic protein was performed. Our results showed that a single injection of MSCs (either preemptive/or post-CCI) produced equipotent effects on allodynia, mechanical hyperalgesia, and thermal response. Immunohistochemical analysis showed that the stem cells have reached the cerebral cortex. The injected group with MSCs before CCI showing few stem cells expressed PCNA, CD117, and nestin in the cerebral cortex. The group injected with MSCs after CCI, showing numerous recently proliferated CD117-, nestin-, PCNA-positive stem cells in the cerebral cortex. In conclusion, our findings demonstrate that the most probable effect of i.v. stem cells is the central anti-inflammatory effect, which opens concerns about how stem cells circulating in systemic administration to reach the site of injury.

Sequencing batch reactor technology for landfill leachate treatment: A state-of-the-art review.

Landfill has become an underlying source of surface and groundwater pollution if not efficiently managed, due to the risk of leachate infiltration into to land and aquifers. The generated leachate is considered a serious environmental threat for the public health, because of the toxic and recalcitrant nature of its constituents. Thus, it must be collected and appropriately treated before being discharged into the environment. At present, there is no single unit process available for proper leachate treatment as conventional wastewater treatment processes cannot achieve a satisfactory level for degrading toxic substances present. Therefore, there is a growing interest in examination of different leachate treatment processes for maximum operational flexibility. Based on leachate characteristics, discharge requirements, technical possibilities, regulatory requirements and financial considerations, several techniques have been applied for its degradation, presenting varying degrees of efficiency. Therefore, this article presents a comprehensive review of existing research articles on the pros and cons of various leachate degradation methods. In line with environmental sustainability, the article stressed on the application and efficiency of sequencing batch reactor (SBR) system treating landfill leachate due to its operational flexibility, resistance to shock loads and high biomass retention. Contributions of integrated leachate treatment technologies with SBR were also discussed. The article further analyzed the effect of different adopted materials, processes, strategies and configurations on leachate treatment. Environmental and operational parameters that affect SBR system were critically discussed. It is believed that information contained in this review will increase readers fundamental knowledge, guide future researchers and be incorporated into future works on experimentally-based SBR studies for leachate treatment.

Adherence to osteoporosis therapy after an upper extremity fracture: a pre-specified substudy of the C-STOP randomized controlled trial.

Despite their proven efficacy for secondary fracture prevention, long-term adherence with oral bisphosphonates is poor. INTRODUCTION: To compare the effectiveness of two interventions on long-term oral bisphosphonate adherence after an upper extremity fragility fracture. METHODS: Community-dwelling participants 50 years or older with upper extremity fragility fractures not previously treated with bisphosphonates were randomized to either a multi-faceted patient and physician educational intervention (the active control arm) vs. a nurse-led case manager (the study arm). Primary outcome was adherence (taking > 80% of prescribed doses) with prescribed oral bisphosphonates at 12 months postfracture between groups; secondary outcomes included rates of primary non-adherence and 24-month adherence. We also compared quality of life between adherent and non-adherent patients. RESULTS: By 12 months, adherence with the initially prescribed bisphosphonate was similar (p = 0.96) in both groups: 38/48 (79.2%) in the educational intervention group vs. 66/83 (79.5%) in the case manager arm. By 24 months, adherence rates were 67% (32/48) in the educational intervention group vs. 53% (43/81) in case managed patients (p = 0.13). Primary non-adherence was 6% (11 patients) in the educational intervention group and 12% (21 patients) in the case managed group (p = 0.07). Prior family history of osteoporosis (aOR 2.1, 95% CI 1.0 to 4.4) and being satisfied with current medical care (aOR 2.3, 95% CI 1.1 to 4.8) were associated with better adherence while lower income (aOR 0.2, 95% CI 0.1 to 0.6, for patients with income < $30,000 per annum) was associated with poorer rates of adherence. There were no differences in health-related quality of life scores at baseline or during follow-up between patients who were adherent and those who were not. CONCLUSION: While both interventions achieved higher oral bisphosphonate adherence compared to previously reported adherence rates in the general population, primary non-adherence and long-term adherence to bisphosphonates were similar in both arms. Adherence was influenced by family history of osteoporosis, satisfaction with current medical care, and income. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01401556.

Bioaccumulation of arsenic and fluoride in vegetables from growing media: health risk assessment among different age groups.

The current study was conducted to evaluate the arsenic (As) and fluoride (F-) concentrations in growing media (stored rainwater and soil), of district Tharparkar, Pakistan. The bioaccumulation/transportation of As and F from growing media to different types of vegetables (wild cucumis, Indian squish and cluster bean) was evaluated. Total concentrations of As and F- in stored rainwater samples were observed up to 585 µg/L and 32.4 mg/L, respectively, exceeding many folds higher than WHO provisional guideline values. The As and F- contents in soil samples of nine agricultural sites were found in the range of 121-254 mg/kg and 115-478 mg/kg, respectively. The highest contents of As and F- were observed in wild cucumis as compared to Indian squish and cluster bean (p < 0.05), grown in the same agricultural field. The bioaccumulation factors of As and F- were to be > 4.00, indicating the high rate of transportation of As and F- from growing media to vegetables. A significant positive correlation of As and F- in vegetables with their concentrations in soil and water was observed (r > 0.60 with p < 0.05). The risk assessment elucidated that the population of different age group consuming local vegetables and drinking water contaminated with As and F- may have adverse health effects.

Paediatric cataract surgery in Hospital Kuala Lumpur - A 5-year review of visual outcomes.

INTRODUCTION: Paediatric cataract surgery is challenging with reported post-operative visual acuity (VA) of 0.3LogMar or better varying between 33% to 68% of patients. OBJECTIVE: The aim is to document the post-operative refraction, VA and complications of non-traumatic pediatric cataract surgery performed in a tertiary referral center in Malaysia. METHODOLOGY: This retrospective study reviewed case notes of all consecutive patients aged 12 years and below who underwent cataract surgery from January 2010 to December 2015. Patients were recruited if they had a minimum of six months post-operative follow-up. Exclusion criteria included traumatic cataract, central nervous system abnormalities, incomplete medical records or pre-existing ocular pathology. Subjects were divided into two groups based on refraction at one month. Subjects with refraction within 1- dioptre of the targeted spherical equivalent were in the success group and the rest were in the failure group. RESULTS: A total of 111 subjects were recruited (65 subjects in success group and 46 subjects in the failure group). Mean age at surgery was 33.14 (SD: 33.47) months. The success group had significantly longer axial length (p:0.0045, CI: 0.566-0.994, OR: 0.750). At final review, 44.1%(49/111) subjects had visual acuity of 0.3LogMar or better. The success group had better final mean VA in comparison to the failure group (p:0.034, CI:1.079-7.224, OR: 2.791). CONCLUSION: The outcome of non-traumatic paediatric cataract surgery was acceptable with 58.6% achieved targeted refractive correction at 1-month post-operative period. Longer axial length was associated with better refractive outcome. Capsule related complications was the most common intra-operative complication.

Changes on physicochemical and rheological properties of biscuits substituted with the peel and alcohol-insoluble solids (AIS) from cactus pear (Opuntia ficus-indica).

Cactus pear fruit consists of the peel, seeds and pulp. The peel is a major waste in cactus pear pulp based products accounting about 37.72% of the fruit weight. The aim of this study was to utilized and characterized the physicochemical and rheological properties of biscuits substituted with extracted cactus pear peel (CPP) and alcohol-insoluble solids (AIS) from cactus pear (Opuntia ficus-indica). To prepare AIS, peels were shredded and dropped in ethanol (70%) for 15 min. The mixture was boiled at 70 °C for 30 min, filtered and washed with ethanol 70% and the washing repeated until no sugars. The residue was washed and dried at room temperature. Changes in physiochemical and rheological properties of extracted CPP and AIS from cactus pear to qualify determine their use in the production of them to produce a fiber-rich food product. The water-holding capacity was 3.7 ml/g for the peel and 1.5 ml/g for the AIS, and the oil-holding capacity was approximately the same for both the CPP and AIS. The protein content was 3.5% for the CPP and 3.72% for the AIS. The CPP and AIS contained little fat (1.22% and 1.44%, respectively). Potassium and calcium in the AIS had the highest concentration, at 21.49 g/kg and 44.04 g/kg, respectively, and these minerals were found at 22.07 g/kg and 16.66 g/kg, respectively, in the CPP. The dominant phenolic compounds found in the CPP were pyrogallol, catechol, catechin, and alpha-coumaric acid. The results showed that the AIS contained pyrogallol (61.67 ppm), benzoic acid (10.68 ppm), vanillic acid (7.66 ppm), catechin (4.65 ppm) and salicylic acid (4.51 ppm). The CPP was rich in glucose (25.95%) and fructose (21.36%) compared to the AIS. The sensory evaluation indicated that 7.5% dried cactus pear peel or 7.5% AIS can be successfully used in substitution of wheat flour biscuits. It could be conducted cactus pear as major by-product can be important for the industrial utilization.

Reactive Astrogliosis in an Experimental Model of Fibromyalgia: Effect of Dexmedetomidine.

To our knowledge, this is the first study which investigates the induction of neuroinflammation in rats using an acidic-saline model of fibromyalgia. It is well known that the hippocampus has a fundamental role in pain perception, and astrocytes play a crucial role in pain signaling. Our aim is to evaluate the ability of dexmedetomidine to attenuate the inflammatory responses induced in astrocytes. In a group of healthy rats, induction of chronic muscle pain by intramuscular injection of 100 µL of acidic saline on days 0 and 5 resulted in peripheral sensitization (measured using the von Frey test) and significant (p < 0.05) increases in IL-1ß (160.2 ± 1.1 to 335.2 ± 1.8), IL-6 (100.1 ± 1.4 to 202.4 ± 1.1), and TNF-α (60.0 ± 0.7 to 115.5 ± 1). Light and electron microscopy revealed degenerative changes in the hippocampus and reactive astrogliosis. Immunohistochemistry showed increased expression of glial fibrillary acid protein and inducible nitric oxide synthase. Surprisingly, treatment with a single dose of an α2-adrenergic agonist, dexmedetomidine (5 µg/kg i.p.), attenuated these changes. This trial suggests that dexmedetomidine possibly directly acts on astrocytes, and a peripheral action is also suggested.

Genetic heterogeneity in Pakistani microcephaly families revisited.

Autosomal recessive primary microcephaly (MCPH) is a rare and heterogeneous genetic disorder characterized by reduced head circumference, low cognitive prowess and, in general, architecturally normal brains. As many as 14 different loci have already been mapped. We recruited 35 MCPH families in Pakistan and could identify the genetic cause of the disease in 31 of them. Using homozygosity mapping complemented with whole-exome, gene panel or Sanger sequencing, we identified 12 novel mutations in 3 known MCPH-associated genes - 9 in ASPM, 2 in MCPH1 and 1 in CDK5RAP2. The 2 MCPH1 mutations were homozygous microdeletions of 164,250 and 577,594 bp, respectively, for which we were able to map the exact breakpoints. We also identified four known mutations - three in ASPM and one in WDR62. The latter was initially deemed to be a missense mutation but we demonstrate here that it affects splicing. As to ASPM, as many as 17 out of 27 MCPH5 families that we ascertained in our sample were found to carry the previously reported founder mutation p.Trp1326*. This study adds to the mutational spectra of four known MCPH-associated genes and updates our knowledge about the genetic heterogeneity of MCPH in the Pakistani population considering its ethnic diversity.

Manipulating mammalian cell morphologies using chemical-mechanical polished integrated circuit chips.

Tungsten chemical-mechanical polished integrated circuits were used to study the alignment and immobilization of mammalian (Vero) cells. These devices consist of blanket silicon oxide thin films embedded with micro- and nano-meter scale tungsten metal line structures on the surface. The final surfaces are extremely flat and smooth across the entire substrate, with a roughness in the order of nanometers. Vero cells were deposited on the surface and allowed to adhere. Microscopy examinations revealed that cells have a strong preference to adhere to tungsten over silicon oxide surfaces with up to 99% of cells adhering to the tungsten portion of the surface. Cells self-aligned and elongated into long threads to maximize contact with isolated tungsten lines as thin as 180 nm. The orientation of the Vero cells showed sensitivity to the tungsten line geometric parameters, such as line width and spacing. Up to 93% of cells on 10 µm wide comb structures were aligned within ± 20° of the metal line axis. In contrast, only ~22% of cells incubated on 0.18 µm comb patterned tungsten lines were oriented within the same angular interval. This phenomenon is explained using a simple model describing cellular geometry as a function of pattern width and spacing, which showed that cells will rearrange their morphology to maximize their contact to the embedded tungsten. Finally, it was discovered that the materials could be reused after cleaning the surfaces, while maintaining cell alignment capability.