Directional control of neurite outgrowth: emerging technologies for Parkinson's disease using magnetic nanoparticles and magnetic field gradients.

A challenge in current stem cell therapies for Parkinson's disease (PD) is controlling neuronal outgrowth from the substantia nigra towards the targeted area where connectivity is required in the striatum. Here we present progress towards controlling directional neurite extensions through the application of iron-oxide magnetic nanoparticles (MNPs) labelled neuronal cells combined with a magnetic array generating large spatially variant field gradients (greater than 20 T m-1). We investigated the viability of this approach in both two-dimensional and organotypic brain slice models and validated the observed changes in neurite directionality using mathematical models. Results showed that MNP-labelled cells exhibited a shift in directional neurite outgrowth when cultured in a magnetic field gradient, which broadly agreed with mathematical modelling of the magnetic force gradients and predicted MNP force direction. We translated our approach to an ex vivo rat brain slice where we observed directional neurite outgrowth of transplanted MNP-labelled cells from the substantia nigra towards the striatum. The improved directionality highlights the viability of this approach as a remote-control methodology for the control and manipulation of cellular growth for regenerative medicine applications. This study presents a new tool to overcome challenges faced in the development of new therapies for PD.

A cross-sectional population survey of physicians in Alberta, Canada about a novel provincial contact tracing smartphone app.

BACKGROUND: The Canadian province of Alberta released the ABTraceTogether smartphone app in May 2020 to assist in contact tracing during the SARS-CoV-2 pandemic. Public engagement with this public health tool has been low, limiting the effectiveness of the intervention. This study examines physician knowledge of the app and practice patterns in relation to the app. METHODS: We conducted a cross-sectional self-administered online English language survey of physicians and medical students in Alberta, Canada. The survey link was sent to all registered members of the College of Physicians and Surgeons of Alberta and was distributed by other provincial physician organizations and health zone leaders. RESULTS: The survey received 317 responses. 96% of participants were aware of the app but only 27% had recommended the app to patients. The most common reason provided for not downloading or recommending the app was that participants had security concerns about the app. 23% of participants indicated they did not believe they had a responsibility to recommend the app to others. CONCLUSIONS: Our study provides insights into participants' knowledge and beliefs about the ABTraceTogether app. This information may be valuable to public health officials who wish to engage physicians in future public health campaigns.

Blood pressure levels and hypertension prevalence in a high selenium environment: results from a cross-sectional study.

BACKGROUND AND AIMS: Recent human and laboratory studies have suggested the possibility that selenium overexposure may increase blood pressure. We sought to ascertain whether adults living in a seleniferous area exhibit an association between selenium exposure and both blood pressure levels as well as prevalence of hypertension. METHODS AND RESULTS: We measured selenium levels in blood (serum), hair and nail samples obtained from 680 adult volunteers (267 men and 413 women), living in seven Punjabi villages in a seleniferous area and related them to health outcomes, including systolic and diastolic blood pressure and presence of hypertension. In a multivariable restricted cubic spline regression model, adjusted for age, sex and history of hypertension, we found a positive association between systolic blood pressure and both serum (P = 0.004) and hair (P = 0.058) selenium levels, but not with nail selenium content. Little association emerged between the three selenium biomarkers and diastolic blood pressure. Hypertension prevalence was positively associated with the three exposure indicators (P < 0.001). The associations we found were generally stronger in women than in men. CONCLUSIONS: Overall, these findings suggest that chronic overexposure to environmental selenium may increase blood pressure, though there were inconsistencies for this association according to the choice of exposure indicator, the study endpoint and the sex.

Subacromial Impingement Syndrome of the Shoulder: A Musculoskeletal Disorder or a Medical Myth?

Subacromial impingement syndrome (SAIS) is a commonly diagnosed disorder of the shoulder. Though this disorder has been known for a long time, it remains a poorly understood entity. Over the years several hypotheses have been put forward to describe the pathogenesis of SAIS but no clear explanation has been found. Two mechanisms, the extrinsic and intrinsic mechanism, have been described for the impingement syndrome. The intrinsic mechanism theories which deny the existence of impingement are gaining popularity in recent years. The various shoulder tests used to diagnose SAIS have low specificity with an average of about 50%. Meta-analysis shows that neither the Neer sign nor the Hawkins sign has diagnostic utility for impingement syndrome. Several randomised controlled trials have shown that the outcome of treatment of SAIS by surgery is no better than conservative treatment. Physiotherapy alone can provide good outcome which is comparable to that achieved with surgery without the costs and complications associated with surgery. Since decompression with surgery does not provide any additional benefits as compared to conservative treatment for patients with SAIS, the impingement theory has become antiquated and surgical treatment should have no role in the treatment of such patients. There are calls by some practitioners to abandon the term impingement syndrome and rename it as anterolateral shoulder pain syndrome. It appears that SAIS is a medical myth. There are others who called SAIS as a clinical illusion.

Graduated Compression Stockings as an Adjunct to Low Dose Low Molecular Weight Heparin in Venous Thromboembolism Prevention in Surgery: A Multicentre Randomised Controlled Trial.

BACKGROUND: The evidence base upon which current global venous thromboembolism (VTE) prevention recommendations have been made is not optimal. The cost of purchasing and applying graduated compression stockings (GCS) in surgical patients is considerable and has been estimated at £63.1 million per year in England alone. OBJECTIVE: The aim was to determine whether low dose low molecular weight heparin (LMWH) alone is non-inferior to a combination of GCS and low dose LMWH for the prevention of VTE. METHODS: The randomised controlled Graduated compression as an Adjunct to Pharmacoprophylaxis in Surgery (GAPS) Trial (ISRCTN 13911492) will randomise adult elective surgical patients identified as being at moderate and high risk of VTE to receive either the current "standard" combined thromboprophylactic LMWH with GCS mechanical thromboprophylaxis, or thromboprophylactic LMWH pharmacoprophylaxis alone. To show non-inferiority (3.5% non-inferiority margin) for the primary endpoint of all VTE within 90 days, 2236 patients are required. Recruitment will be from seven UK centres. Secondary outcomes include quality of life, compliance with stockings and LMWH, overall mortality, and GCS or LMWH related complications (including bleeding). Recruitment commenced in April 2016 with the seven UK centres coming "on-line" in a staggered fashion. Recruitment will be over a total of 18 months. The GAPS trial is funded by the National Institute for Health Research Health Technology Assessment in the UK (14/140/61).

Spinal Fusion for Chronic Low Back Pain: A 'Magic Bullet' or Wishful Thinking?

Chronic low back pain is a common, disabling and costly health problem. The treatment of chronic low back is difficult and is often ineffective. For treatment to be effective the cause of the pain has to be established but unfortunately in 80% to 95% of the patients the cause cannot be determined despite the existence of modern imaging techniques. A pathoanatomical diagnosis which fits into a classical disease model where successful treatment can be carried out, can only be made in 5% to 7% of the patients. The back pain in the rest of the patients where no pathoanatomical diagnosis can be made is often labelled, unscientifically, as chronic low back pain. Despite the existence of sophisticated imaging techniques and a plethora of diagnostic test the source of pain in patients with nonspecific back pain cannot be established. There exist no causal relationship between imaging findings of degenerated disc, lumbar facet arthritis, spondylosis, spondylolysis and spondylolisthesis, to the pain in these patients. Surgical treatment of non-specific back pain where no pathoanatomical diagnosis has been established is bound to fail. Therefore the outcome of spinal fusion in these patients can be no better than nonsurgical treatment. Spinal fusion is a major surgery which can be associated with significant morbidity and occasionally with mortality. Yet there is rapid rise in the rates of spinal fusion. There is a growing tension between ethics and conflicts of interest for surgeons. The spine, unfortunately, has been labelled as a profit centre and there are allegations of conflicts of interest in the relationship of doctors with the multi-billion dollar spinal devices industry. The devices industry has a significant influence on not only research publications in peer review journals but also on decisions made by doctors which can have a detrimental effect on the welfare of the patient.

"Doc' do I need an anterior cruciate ligament reconstruction? What happens if I do not reconstruct the cruciate ligament?"

We are all aware that there has been a dramatic increase in the number of anterior cruciate ligament (ACL) reconstructions that are carried out here in Malaysia as well as around the world. The numbers of ACL injuries have undoubtedly increased over the years with greater participation of young adults in sporting activities. However it is not certain whether the increase in the numbers of reconstructions can be accounted for by the increasing numbers of ACL injuries. Without doubt commercial interests as well the influence of the biomedical companies have a role to play. In the past the rational for surgical treatment of an ACL tear was that the ACL is vital for knee function and that in the long term ACL deficiency will lead to more injuries of the meniscus and more degeneration of the joint. This belief was prevalent because the natural history of an ACL deficient knee was not known although the ultimate outcome of reconstruction of the ACL was not known either. However in past few years a substantial amount research has been published, which has elucidated the natural history of ACL deficient knees as well as the long term outcome of reconstruction of the ACL.

Selenium distribution and speciation in plant parts of wheat (Triticum aestivum) and Indian mustard (Brassica juncea) from a seleniferous area of Punjab, India.

The concentration, distribution, and speciation of selenium in different parts of wheat and Indian mustard, grown in a seleniferous area in Punjab, were investigated using synchrotron based (XAS) and classical acid digestion and extraction methods. The analyses revealed a high Se enrichment in all investigated plant parts, with Se levels in the range of 133-931 mg/kg (dry weight, dw). Such high Se enrichment is mainly due to the considerable amounts of easily available Se detected in the soil, which are renewed on a yearly basis to some extent via irrigation. Speciation analysis in soil and plants indicated selenate and organic Se as major Se species taken up by plants, with a minor presence of selenite. The analyses also revealed that the highest Se enrichment occurs in the upper plant parts, in agreement with the high uptake rate and mobility of selenate within plants. In both wheat and mustard, highest Se enrichments were found in leaves (387 mg/kg·dw in wheat and 931 mg/kg·dw in mustard). Organic species (dimethylselenide and methylselenocysteine) were found in different parts of both plants, indicating that an active detoxification response to the high Se uptake is taking place through methylation and/or volatilization. The high proportion of selenate in wheat and mustard leaves (47% and 70%, respectively) is the result of the inability of the plant metabolism to completely transform selenate to non-toxic organic forms, if oversupplied. Methylselenocysteine, a common Se species in accumulating plants, was detected in wheat, suggesting that, in the presence of high Se concentration, this plant develops similar response mechanisms to accumulator plants.

Ocular disability--WHO grade 2 in persons affected with leprosy.

Leprosy remains to be a leading cause of peripheral neuropathy and disability. In recent years under Leprosy control programme more stress is being laid on disability assessment. This study was aimed to find prevalence of grade of Ocular disability among persons affected with leprosy (PAL) according to WHO disability grading scale and to find Ocular contributors to grade 2 disability in PAL. A cross sectional study was carried out in tertiary care hospital in Lucknow, Uttar Pradesh. About 302 PAL were interviewed and their eyes clinically examined during 2 years. Data was analysed in percentages, x2 test, Anova. Ocular disability was found in 39.40% persons affected with leprosy (PAL). Of 604 eyes, 13.07% had grade 1 disability and 19.86% had grade 2 disabilities. Bilateral disability was more common than unilateral disability. Ocular disability was more common in PAL with more than one year of leprosy and even higher in those staying in leprasoria (p = 0.012). The most common cause of ocular grade 2 disabilities was corneal involvement (14.23% PAL). Cataract was found to be the most common cause of visual disability (although it is not caused by leprosy). Screening for ocular disability should be incorporated as a routine protocol in PAL to reduce the severity of Ocular disability. Early diagnosis and prompt preventive measure is essential to reduce the burden of visual impairment and blindness in PALthus bringing down the load of grade 2 disability due to leprosy in the society which in itself is an indicator of leprosy control.

"'Doc' do I need an anterior cruciate ligament reconstruction? What happens if I do not reconstruct the cruciate ligament?".

We are all aware that there has been a dramatic increase in the number of anterior cruciate ligament (ACL) reconstructions that are carried out here in Malaysia as well as around the world. The numbers of ACL injuries have undoubtedly increased over the years with greater participation of young adults in sporting activities. However it is not certain whether the increase in the numbers of reconstructions can be accounted for by the increasing numbers of ACL injuries. Without doubt commercial interests as well the influence of the biomedical companies have a role to play. In the past the rationale for surgical treatment of an ACL tear was that the ACL is vital for knee function and that in the long term ACL deficiency will lead to more injuries of the meniscus and more degeneration of the joint. This belief was prevalent because the natural history of an ACL deficient knee and the ultimate outcome of reconstruction of the ACL were both not known. However in recent years a substantial amount of research has been published, which has elucidated the natural history of ACL deficient knees as well as the long term outcome of reconstruction of the ACL.

'VASPFix' for measurement of VASP phosphorylation in platelets and for monitoring effects of P2Y12 antagonists.

Vasodilator-stimulated phosphoprotein (VASP) is phosphorylated and dephosphorylated consequent to increases and decreases in cyclic nucleotide levels. Monitoring changes in VASP phosphorylation is an established method for indirect measurement of cyclic nucleotides. Here we describe the use of an innovative cocktail, VASPFix, which allows sensitive and reproducible measurement of phosphorylated VASP (VASP-P) in a simple, single-step procedure using cytometric bead technology. Frozen VASPFix-treated samples are stable for at least six months prior to analysis. We successfully used VASPFix to measure VASP-P in platelets in both platelet-rich plasma and blood in response to compounds that increase (dibutyryl cAMP, adenosine, iloprost, PGE1) and decrease (ADP, PGE1) cAMP, and to determine the effects of certain receptor antagonists on the results obtained. The change in VASP-P brought about by adding ADP to PGE1-stimulated platelets is a combination of the effect of ADP at the P2Y12 receptor and of PGE1 at both IP and EP3 receptors. For iloprost-stimulated platelets EP3 receptors are not involved. A procedure in which iloprost, ADP and VASPFix were used to determine effectiveness of clopidogrel and prasugrel in patients was compared with an established commercial procedure that uses PGE1 and ADP; the latter produced higher platelet reactivity values that were the result of PGE1 interacting with platelet EP3 receptors. We conclude that VASPFix can be used both as a research tool and for clinical investigations and provides better specificity for P2Y12 receptor inhibition. The latter confers a distinct advantage over existing methods used to monitor effects of P2Y12 antagonists on platelet function.

A study of cardio-metabolic risk profile in patients with psoriasis.

INTRODUCTION/BACKGROUND: Psoriasis is a chronic immune mediated inflammatory disorder of the skin and joints. Recent studies have shown increased prevalence of traditional cardiovascular risk factors such as diabetes mellitus, hypertension and metabolic syndrome. Since atherosclerosis and psoriasis share a common link of inflammation, different workers have shown psoriasis to be a risk factor for atherosclerosis. The aim of our study was assessment of cardiovascular risk factors and evidence of subclinical atherosclerosis in patients of psoriasis. METHODS: In a hospital based, cross-sectional study, 96 patients with psoriasis and 100 age, sex and weight matched controls were enrolled. Prevalence of diabetes, hypertension, metabolic syndrome was studied. They were also assessed for endothelial dysfunction by brachial artery flow mediated dilatation(FMD) and carotid intima media thickness (CIMT). RESULTS: There was higher prevalence of hypertension, hypertriglyceridaemia, diabetes mellitus and metabolic syndrome in patients with psoriasis than in controls. FMD was lower in patients with psoriasis than in controls (5.6 +/- 2 vs7.5 +/- 2.8, P = 0.02). The mean CIMT was significantly increased (0.78 +/- 0.12 vs 0.62 +/- 0.08, P = 0.001) in patients with psoriasis compared with controls. In psoriasis patients, CIMT was associated with hypertension, hypertriglyceridaemia, diabetes, insulin resistance, increased severity and duration of psoriasis while in multivariate analysis insulin resistance (OR 2.8, 95% CI 1.92-6.34 P = 0.02) and increased duration of disease (OR 3.12, 95% CI 2.34-7.56) a were the independent risk factors associated with higher CIMT. CONCLUSION: Patients of psoriasis have higher prevalence of metabolic syndrome, cardiovascular risk factors and subclinical atherosclerosis than general population. As a routine, individuals with moderate to severe psoriasis of long duration should be recognised as being at increased cardio vascular risk and thus encouraged for therapeutic interventions to reduce the modifiable risk factors.

Variation in buccal surface morphology of deciduous first molars.

BACKGROUND: The buccal bulge of the deciduous first molars has always been a restorative challenge to the pediatric dentist. Morphologically it may vary from a slight prominence to a well-developed cusp-like structure. AIM: This study was conducted to determine the variable buccal surface morphology of deciduous first molar and its clinical relevance. MATERIALS AND METHODS: A prospective study was conducted whereby 2016 patients visiting the outpatient clinic of dental hospital over 1 year were evaluated. Any variation in buccal surface morphology of the deciduous first molars was recorded photographically or by replicating in dental stone. RESULTS: Varied morphological patterns on buccal surface were observed for which a new classification scheme has been proposed. CONCLUSION: The surface morphology of deciduous teeth crowns must be studied carefully as it may be indicative of pulpal extensions and accessory roots, requiring consideration during restorative treatment planning.

Developing a sustainable phytomanagement strategy for excessive selenium in western United States and India.

Phytomanagement technology is recognized as an inexpensive and environmental friendly strategy for managing natural-occurring selenium (Se) in soils and in poor quality waters. Multi-year field and greenhouse studies were conducted with different plant species in California, USA and Punjab, India under high Se growing conditions. Some of the plant species included; canola (Brassica napus), mustard (B. juncea), broccoli (B. oleracea), spearmint (Mentha viridis), sugarcane (Saccharum officcinarum), guar (Cyamopsis tetragonoloba), wheat (Triticum aestivum), and poplar (Populus deltoides). California soils had a sodium-sulfate-dominated salinity between 6-10 dS m(-1), while Indian soils had a calcium carbonate salinity less than 1 dS m(-1). Results demonstrated that high sulfate conditions reduced plant Se accumulation more than 100 x in Californian grown plants compared to Se accumulation in Indian grown plants. Tissue concentrations generally did not exceed 10 and 200 mg kg DM(-1) in leaves of plants grown in California and India, respectively. At these plant concentrations, Se phytomanagement is more effective in Indian soils than in California soils. Successful management of Se by plants requires selecting crops or crop rotations that are tolerant of the soil condition and identifying and creating new viable Se-enriched products.

Selenium accumulation by forage and grain crops and volatilization from seleniferous soils amended with different organic materials.

Greenhouse and field experiments were conducted to study the direct and residual effect of applying different organic materials on Se accumulation by crops and volatilization from seleniferous soils of northwestern India. Among organic manures, press mud and poultry manures proved 4-5 times more effective in reducing Se accumulation by different crops than farmyard manure. Efficiency of organic manures increased with increase in application rates. Application of both press mud and poultry manures reduced Se accumulation by 44-97% in wheat (Triticum aestivum) and rapeseed (Brassica napus) shoots in the greenhouse; 85-92% in wheat straw, 45-74% in wheat grains, 45-74% in rapeseed straw and 76-92% in rapeseed grains under field conditions. Both the manures remained highly effective in reducing Se accumulation by the crops following wheat and rapeseed and the extent of reduction varied from 50% to 87% in maize (Zea mays) and cowpeas (Vigna sinensis) in the greenhouse and 40-89% in maize and rice (Oryza sativa) crops under field situation. Rate of Se volatilization by wheat and rapeseed crops increased by 1.8-4.0 times; the greatest increase was observed with press mud followed by poultry manure, arhar (Cajanus cajan) leaves and farmyard manure. After 134d of incubation of 500g soil amended with 2% of plant tissues, the maximum amount of Se was volatilized with cowpea leaves (385ng) followed by wheat grains, leaves of maize, sugarcane (Saccharum officcinarum), arhar, poplar (Populus deltoides) and the control (91ng). The results of this study convincingly prove the usefulness of applying press mud and poultry manure in enhancing volatilization and retarding the transfer of Se from soil to plant in seleniferous soils.

Bioavailability of selenium to forage crops in a sandy loam soil amended with Se-rich plant materials.

Greenhouse experiments were conducted to study the bioavailability of selenium (Se) to sorghum (Sorghum bicolor L.), maize (Zea mays L.) and berseem (Trifolium alexandrinum L.) fodders in a sandy loam soil amended with different levels of Se-rich wheat (Triticum aestivum L.) and raya (Brassica juncea L. Czern) straw containing 53.3 and 136.7microg Seg(-1), respectively. Each of the fodder crops was grown after incorporation of Se-rich materials either individually or in a sequence - sorghum-maize-berseem by incorporating Se-rich straws only to the first crop. Application of Se-rich straws to each crop, even at the greatest rate of 1%, did not have any detrimental effect on dry matter yield of different crops. With increase in the level of wheat straw from 0% to 1%, Se content in sorghum and maize plants increased to greatest level of 1.3 and 1.5microg g(-1), respectively, at 0.3% of applied straw and thereafter it decreased consistently. In case of raya straw, the greatest Se content in sorghum (2.3microg g(-1)) and maize (3.0microg g(-1)) was recorded at 0.3% and 0.4% of the applied straw, respectively. Unlike sorghum and maize fodders, Se content in all the four cuts of berseem continued to increase with increase in the level of applied straws and for different cuts of berseem it varied from 1.6 to 2.3 and 3.4 to 4.3microg g(-1) in case of wheat and raya straw, respectively. Similar variations in Se content of different fodder crops were recorded when these were grown in the sequence - sorghum-maize-berseem; but Se content was 2-4 times lower than when each crop was grown with fresh application of Se-rich straw. None of the fodders absorbed Se in levels toxic for animal consumption (>5microg g(-1)) even at the greatest level of applied straw. Of the total Se added through Se-rich straws, utilization of Se was not more than 2% in case of sorghum and maize crops and up to 5% in case of berseem. At the time of sowing of sorghum, hot water soluble Se (HWS-Se) in soils treated with different levels of Se-rich wheat and raya straw, respectively, varied from 18 to 36 and 18 to 79microg kg(-1). Whereas in case of berseem, it varied from 33 to 101 and 33 to 154microg kg(-1), respectively. HWS-Se present at the sowing time of berseem was significantly correlated with Se content of all the four cuts in the soil treated with Se-rich straws; the coefficients of correlation 'r' varied between 0.79 (p0.05) and 0.99 (p0.001). Selenium-rich materials supplied significant amounts of S, P and micronutrients to the growing fodder crops. These investigations suggest that Se-rich raya and wheat straw may be disposed off safely in soils used for growing fodders.

Dietary selenium intake by men and women in high and low selenium areas of Punjab.

OBJECTIVE: To determine the selenium intake of adults residing in high and low selenium areas of rural Punjab. DESIGN: All food samples consumed by the subjects were collected and analysed for selenium content. Based on food intake data and selenium content of foods, the selenium intake of the subjects was calculated. Hair, fingernails and urine samples from a sub-sample of subjects were collected and analysed for selenium. SETTING: Three villages from the selenium-endemic area of Nawan Shahr District and two villages from the non-endemic area of Ludhiana District, Punjab, India, were covered. SUBJECTS: Forty families from each of the two areas, with one adult male and one adult female in the age range of 20-40 years, were surveyed. Thus a total of 80 men and 80 women constituted the study sample. RESULTS: In the selenium-endemic area, the average selenium intake of both men and women was more than nine times that in the non-endemic area and exceeded the maximum tolerable limit in more than 60% of men. Mean selenium content of the hair, nails and urine of both men and women was tens of times higher than in the non-endemic area. CONCLUSIONS: High selenium intake in the endemic area resulted in high selenium content in the hair, nails and urine of men and women. In addition, clinical symptoms of selenium toxicity were also observed in some of the subjects. Selenium intake in the non-endemic area was marginally below the suggested value. Based on the study results, steps need to be taken to educate the public in the endemic area to avoid selenium toxicity.