Multiple Intravenous Administrations of Human Umbilical Cord Blood Cells Benefit in a Mouse Model of ALS

Background: A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25x10(6) cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages. Methodology/Principal Findings: Mice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 10(6) or 2.5x10(6) cells from 13 weeks of age. A third, pre-symptomatic, group received 10(6) cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 10(6) cells pre-symptomatically or 2.5x10(6) cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups. Conclusions/Significance: These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies

Reasons of using complementary and alternative medicines (CAM) among elderly Malaysians of Kuala Lumpur and Selangor states: an exploratory study

Background: This study is aimed to explore the types of CAM and reasons of using CAM among elderly Malaysians. Method: This cross-sectional study was conducted on a sample of 256 conveniently selected elderly Malaysians who were residing in the states of Selangor and Kuala Lumpur. A pre-validated interviewadministered questionnaire was used to gather information. Data was entered into PASW version 18 and analyzed. Results: A total of 256 questionnaires were included in the study. A response rate of 64% was achieved. Out of 256 respondents, 92 (35.9%) were male while 164 (64.1%) were female. More than half of the respondents (n ¼ 141; 55.1%) agreed that CAM is more effective than allopathic medicine. Chinese respondents showed strong belief in the effectiveness of CAM. In terms of safety of CAM, close to three quarters of respondents (n ¼ 178; 69.5%) believed that CAM is safer than allopathic medicine. A large majority of respondents agreed that CAM has less side effects compared to allopathic medicine (n ¼ 201; 78.5%) and also agreed that CAM is good to maintain overall health and wellbeing (n ¼ 212; 82.8%). A majority of the respondents expressed that they use CAM because allopathic medicine is less effective (n ¼ 113; 44.1%). Conclusion: The current study reflects the reasons of using CAM among lay public from different ethnicities. There are no reports of adverse effects related to CAM use. Future approaches should be intended for awareness campaigns for consumers, highlighting safety profile of CAM and as well as forbidding their use without the consultation of healthcare professional

Use and perceived benefits of mouthwash among Malaysian adults: An exploratory insight

Objectives: The purpose of the current research is to comprehend the use as well as the perception of mouthwash benefits among Malaysian adults in Selangor state, Malaysia. Materials and Methods: Questionnaires were distributed following convenience sampling to 400 respondents in public places around Selangor over a period of 3 months. The questions were divided into 4 main categories which were demographics, behavior, knowledge, and perceived benefits. The data collected were entered into PASW version 20 and analyzed. Descriptive and inferential statistics were applied. Chi-square was used to compute the association between the variables. Results: The majority of the respondents (n = 178, 44.5%) were between the ages of 18-25 years. Female respondents outnumbered males with 243 (60.8%) and 157 (39.3%), respectively. There was a high level of awareness among the respondents regarding the use of mouthwash where more than 57% answered the knowledge questions correctly. When asked for the reason for using a particular brand, respondents stated that their selection depends on it being "a family brand", affordability and taste. Respondents had a good perception on the use of mouthwash and its benefits. Conclusion: The public needs to be educated on the role of mouthwash. Knowledge gaps on mouthwash need to be bridged to ascertain the beneficial nature of mouthwash. A mixed method research is recommended to gather more information on oral hygiene practices among Malaysian general population, particularly focusing on the use of mouthwash

Identifying Symptom Information in Clinical Notes Using Natural Language Processing.

BackgroundSymptoms are a core concept of nursing interest. Large-scale secondary data reuse of notes in electronic health records (EHRs) has the potential to increase the quantity and quality of symptom research. However, the symptom language used in clinical notes is complex. A need exists for methods designed specifically to identify and study symptom information from EHR notes.ObjectivesWe aim to describe a method that combines standardized vocabularies, clinical expertise, and natural language processing to generate comprehensive symptom vocabularies and identify symptom information in EHR notes. We piloted this method with five diverse symptom concepts: constipation, depressed mood, disturbed sleep, fatigue, and palpitations.MethodsFirst, we obtained synonym lists for each pilot symptom concept from the Unified Medical Language System. Then, we used two large bodies of text (clinical notes from Columbia University Irving Medical Center and PubMed abstracts containing Medical Subject Headings or key words related to the pilot symptoms) to further expand our initial vocabulary of synonyms for each pilot symptom concept. We used NimbleMiner, an open-source natural language processing tool, to accomplish these tasks and evaluated NimbleMiner symptom identification performance by comparison to a manually annotated set of nurse- and physician-authored common EHR note types.ResultsCompared to the baseline Unified Medical Language System synonym lists, we identified up to 11 times more additional synonym words or expressions, including abbreviations, misspellings, and unique multiword combinations, for each symptom concept. Natural language processing system symptom identification performance was excellent.DiscussionUsing our comprehensive symptom vocabularies and NimbleMiner to label symptoms in clinical notes produced excellent performance metrics. The ability to extract symptom information from EHR notes in an accurate and scalable manner has the potential to greatly facilitate symptom science research

Use of oral cleaning devices and their perceived benefits among Malaysians in Kuala Lumpur and Johor Bahru: An exploratory structured approach

Background and Objectives: Various devices have been used to maintain oral hygiene. These include toothbrush and toothpaste, mouthwash, dental floss, miswak, and toothpick. This study attempts to investigate the use of various oral cleaning devices and their perceived benefits among Malaysians. Methods: A quantitative cross-sectional study conducted in two different cities of Malaysia. A convenience sampling approach was adopted. A total of 787 participants agreed to participate in the current research. A validated questionnaire translated into national language was used for data collection. Statistical Analysis Used: Data analysis was performed using Statistical Package for Social Sciences version 20. Results: About 302 respondents were in the age range of 18 – 25 years old (38.4%). There were marginally more females (55.7%) than males (44.3%). Although 99.9% of the participants used a toothbrush, a significant majority (n = 590, 75%) used more than a single device to maintain their oral hygiene. Only 311 respondents knew that toothpicks were inappropriate to use to remove food between teeth and gums, while a majority (n = 592, 75.2%) did not realize that some mouthwashes can stain the teeth. Less than half (42.1%) knew that improper use of miswak might harm the teeth. Conclusions: Although their oral hygiene behaviors are relatively at a higher level, their perceived oral health benefits did not compare well

Use and perceived benefits of mouthwash among Malaysian adults: an exploratory insight

This study aimed to explore the use and perceived benefits of mouthwash among Malaysian adults. Method: This is a cross-sectional study which was conducted in public places around the states of Selangor and Penang, Malaysia. It is a questionnaire-based study which was conducted as face-to-face interview. A convenience sample of 792 mouthwash users was recruited in 2013 in an ethically approved study (International Medical University). The study instrument was formulated on the basis of literature search and subjected to 20 experts for validation purpose. A pilot study was conducted to compute Cronbach Alpha (0.78). Data was entered into PASW version 20. Descriptive and inferential statistics were applied. Results: A response rate of 99% was achieved. More than two third of the respondents are female, suggesting women are more likely to use mouthwash (n ¼486; 61.8 %). The major reason to use mouthwash were to mask halitosis (n¼287; 36.5%) and to prevent oral diseases (n¼243; 30.9%). Majority knew that fluoride helps in reducing plaque (n¼599; 76.1%) and tooth decay (n¼631; 80.2%). Respondents were not clear that only tooth brushing alone is insufficient to prevent gum disease (n¼553; 70.3%). More than two thirds perceived that mouthwash is useful in reducing plaque (n¼567; 72.0%) as well as periodontal disease (n¼580; 73.7%). Respondents perceived that mouthwash is more effective in eliminating halitosis (n¼714; 90.7%) and preventing caries (n¼630; 80.1%). The frequency of mouthwash use was statistically significant with age, gender, race and monthly income (p¼0.018. 0.091, 0.010, 0.030) . Conclusion: This study indicates that Malaysian adults have good knowledge on the use and perceived benefits of mouthwash. A nationwide study is advocated to gather more information from general population, targeting the use of mouthwash in a large scale to minimize oral health problems

Characteristics of motor neuron survival in the spinal cord of G93A mice.

<p>Motor neuron counts were performed in the cervical (<b>A</b>) and lumbar (<b>B</b>) ventral horns of G93A mice at 17 weeks of age and at end-stage of disease. Mice receiving 2.5×10⁶ cells symptomatically (<i>Gr 1</i>) or 1×10⁶ cells pre-symptomatically (<i>Gr 3</i>) had significantly higher motor neuron densities than the Media group (<i>Gr 4</i>) at 17 weeks of age or at end-stage of disease. In both cervical and lumbar spinal cords, motor neuron densities between <i>Gr 2</i> (1×10⁶ cells, symptomatic) and Media-injected (<i>Gr 4</i>) mice showed no significant differences (p>0.05). *p<0.05, **p<0.01, ***p<0.001. (<b>C</b>) Immunohistochemical staining of motor neurons in the lumbar spinal cord of G93A mice at 17 weeks of age. Motor neuron staining for anti-choline acetyltransferase (anti-ChAT) antibody showed healthy motor neurons in controls (<b>a</b>) although only a few neurons survived in the Media-treated animals (<b>b</b>). Cell-treated mice with (<b>c</b>) 2.5×10⁶ cells symptomatically (<i>Gr 1</i>) and (<b>e</b>) 1×10⁶ cells pre-symptomatically (<i>Gr 3</i>) demonstrated higher motor neuron survival than (<b>d</b>) mice receiving 1×10⁶ cells symptomatically (<i>Gr 2</i>). Scale bar: a–e is 50 µm.</p

Evaluations of disease progression in G93A mice through Kaplan-Meier analysis.

<p>(<b>A</b>) Time elapsed until animals lost 15% of their maximum body weight. Mice receiving 1×10⁶ cells pre-symptomatically (<i>Gr 3</i>) significantly () maintained body weight vs. Media (<i>Gr 4</i>) mice. A similar trend was observed in mice treated with 2.5×10⁶ cells (<i>Gr 1</i>) beginning at symptomatic disease stage. (<b>B</b>) Time elapsed until hindlimb extension scores deteriorated by 70% of the initial score. The <i>Gr 1</i> and <i>Gr 3</i> mice significantly () delayed decline of hindlimb extension compared to <i>Gr 4</i> mice. A significant difference was also detected between <i>Gr 3</i> and <i>Gr 2</i> mice receiving 1×10⁶ cells at pre-symptomatic or symptomatic stage of disease, respectively. (<b>C</b>) Time elapsed until muscle strength decreased by 70% from the maximum value. Mice from <i>Gr 3</i> significantly () delayed muscle strength losses vs. <i>Gr 4</i>. <i>Gr 1</i> mice tended to maintain muscle strength post-transplant. (<b>D</b>) Time elapsed until rotarod latency decreased by 70% of the maximum value. Only mice from <i>Gr 3</i> performed better on the rotarod than other cell-treated mice and tended towards significance () taking more time to decrease latency by over 70% of the maximum value compared to <i>Gr 4</i>.</p

Distribution of MNC hUCB cells in the spinal cord of G93A mice.

<p>Administered MNC hUCB cells were identified immunohistochemically by a human-specific marker (HuNu) in the spinal cord of cell-treated mice at 17 weeks of age, 4 weeks (symptomatic) or 8 weeks (pre-symptomatic) post-transplant. In the total area of cervical (<b>A</b>) and lumbar (<b>B</b>) cervical spinal cord, HuNu positive MNC hUCB cells were found irrespective (p>0.05) of injected cell doses or time beginning treatment. In all cell-treated mice, more than 50% of the observed cells were in ventral horn gray matter. (<b>C</b>) Immunohistochemical staining of MNC hUCB cells in the lumbar spinal cord. MNC hUCB cells positive for HuNu (green, arrow) were detected in the lumbar spinal cord of mice receiving 2.5×10⁶ (<b>a</b>) or 1×10⁶ (<b>b</b>) cells symptomatically or 1×10⁶ cells pre-symptomatically (<b>c</b>). Cells were frequently observed inside the capillary lumen, but also in the spinal cord parenchyma. (<b>a′</b>), (<b>b′</b>), and (<b>c′</b>) are merged images with DAPI. Scale bar: a–c′ is 50 µm.</p

Characteristics of microglial cells in the spinal cords of G93A mice.

<p>Microglial densities were measured in the cervical (<b>A</b>) and lumbar (<b>B</b>) ventral horns of G93A mice at 17 weeks of age and at end-stage of disease. Microglial densities were significantly (p<0.001) higher in Media-injected mice (<i>Gr 4</i>) compared to control mice (<i>Gr 5</i>) of the same ages. MNC hUCB cell administrations significantly (p<0.001) decreased the number of microglia in the spinal cord of G93A mice compared to Media mice. No significant differences were detected between the cell-treated groups. *p<0.05, **p<0.01, ***p<0.001. (<b>C</b>) Immunohistochemical staining of microglia in the lumbar spinal cord at 17 weeks of age. Microglial cells stained for anti-Iba-1 antibody were sparse in controls (<b>a</b>) and microgliosis was noted in Media-treated animals (<b>b</b>). MNC hUCB cells decreased microglial density in mice from <i>Gr 1</i> (<b>c</b>), <i>Gr 2</i> (<b>d</b>), and <i>Gr 3</i> (<b>e</b>). Morphological analysis of microglial cells determined numerous activated cells with large cell bodies and short processes in Media-injected mice, whereas ramified microglia were mostly observed in cell-treated animals, particularly in <i>Gr 1</i> and <i>Gr 3</i> mice and controls (inserts in a–e). Scale bar: a–e is 200 µm; in a–e inserts is 25 µm.</p