Health risk assessment and prevalence of work-related musculoskeletal disorders among the aged brick molders, in India.

The Brickfield Industry is the major and oldest informal industry in India, where millions of brickfield workers make their livelihood. Aged brickfield workers are also involved in different activities in the brickfield, especially in brick mold activities owing to poor socioeconomic conditions. A cross-sectional study was designed to determine the prevalence of work-related musculoskeletal disorders among the aged brick molders and compare them with aged control subjects. A Nordic Questionnaire was applied to assess the discomfort felt among both groups of workers and the Rapid Upper Limb Assessment (RULA) method was used to evaluate posture during their job. The RULA posture analysis showed that the posture adopted by aged brick molders required changes immediately. The result of the ART tool also stated that the brick molding activities' exposure level was high and required further investigation urgently. The study concluded that due to working in a forward bending posture for a prolonged period, aged brickmolders suffered from severe low back and knee pain along with upper-limb disorders due to repetitive activities.

Adverse Health Effects and Perceived Musculoskeletal Pain in the Sawmill Workers of West Bengal, India.

The present study aimed to determine the prevalence of musculoskeletal pain, unfavorable working conditions, and assessment of occupational injuries among sawmill workers. The Nordic Musculoskeletal Questionnaire, measurement of handgrip strength, working environment, and occupational injuries were assessed among 135 sawmill workers participating in the study. The data showed that sawmill workers complained of discomfort (pain) felt primarily in the low back region of the body followed by the shoulders, hands, knees, upper back, and wrist. This study indicated that sawmill workers had less handgrip strength due to more intense manual work than control subjects. Based on the results of this study, it was concluded that sawmill workers were highly affected due to working in an awkward posture with manual material handling for an extended period of time and that these factors may lead to work-related musculoskeletal disorders as well as occupational injuries. Proper training, a proper work-rest schedule, and modifications of some working procedures may reduce injuries and work-related musculoskeletal pain.

D-685 Reverses Motor Deficits and Reduces Accumulation of Human α-Synuclein Protein in Two Different Parkinson's Disease Animal Models.

Aggregation of misfolded α-synuclein (α-syn) protein in the periphery and central nervous system (CNS) gives rise to a group of disorders, which are labeled collectively as synucleinopathies. These clinically distinct disorders are known as pure autonomic failure, Parkinson's disease (PD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). In the case of PD, it has been demonstrated that toxic aggregates of α-syn protein not only cause apoptosis of dopamine neurons but its accumulation in the neocortex and limbic area principally contributes to dementia. In our multifunctional drug discovery research for PD, we converted one of our catechol-containing lead dopamine agonist molecules D-520 into its prodrug D-685. The prodrug exhibited higher in vivo anti-Parkinsonian efficacy in a reserpinized PD animal model than the parent D-520 and exhibited facile brain penetration. In our study with an α-syn transgenic animal model (D line) for PD and dementia with Lewy bodies (DLB), we have shown that 1 month of chronic treatment with the compound D-685 was sufficient to reduce the accumulation of α-syn and phospho-α-syn in the cortex, hippocampus, and striatum areas significantly compared to the control tg mice. Furthermore, D-685 did not exhibit any deleterious effect in the CNS as was evident from the neuron and microglia studies. Future studies will further explore in depth the potential of D-685 to modify disease progression while addressing symptomatic deficits.

Work-related musculoskeletal disorders in agriculture: Ergonomics risk assessment and its prevention among Indian farmers.

BACKGROUND: Indian farmers have musculoskeletal disorders as agriculture is a physically demanding occupation. OBJECTIVES: The main aim of this study is to identify ergonomic and psychosocial risk factors associated with musculoskeletal disorders (MSDs) among different groups of farmers. The other objective is to investigate how MSDs affect farmers' daily lives and interfere with their activities. METHODS: Farmers were evaluated for the repetitiveness of work and MSDs using the standard Nordic questionnaire, ergonomic assessment tool (REBA), and ART tool. RESULTS: Low back portions were the most affected body parts, followed by the knees (OR = 0.352; 95% CI = 0.280-0.598), shoulder (OR = 0.657; 95% CI = 0.405-1.066), neck (OR = 0.510; 95% CI = 0.350-0.743), ankle or foot (OR = 0.815; 95% CI = 0.556-1.196), and upper back region (OR = 0.681; 95% CI = 0.463-1.002). The REBA method found that most of the postures in farming are very dangerous. The ART tool showed that most of the activities are repetitive. Working long hours (90%) and monotony at work (87.5%) are the main psychosocial factors, followed by pressure to finish within a given timeframe (71.4%) and injuries related to MSDs. CONCLUSION: Farmers suffer from musculoskeletal disorders in various body parts (lower back, knee, neck, shoulder, and upper back) due to squatting, stooping, and other constrained working postures during agricultural activities. rolonged working hours, repetitive movements, and MMH are ergonomic risk factors forFurthermore, p MSDs.

Bivalent dopamine agonists with co-operative binding and functional activities at dopamine D2 receptors, modulate aggregation and toxicity of alpha synuclein protein.

To follow up on our previous report on bivalent compounds exhibiting potent co-operative binding at dopamine D2 receptors, we modified the structure of the linker in our earlier bivalent molecules (S)-6-((9-(((R)-5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)nonyl)-(propyl)amino)-5,6,7,8-tetrahydronaphthalen-1-ol (Ia) and (S)-6-((10-(((R)-5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)decyl)(propyl)amino)-5,6,7,8-tetrahydronaphthalen-1-ol (Ib) (Fig. 1) connecting the two pharmaophoric moieties to observe any tolerance in maintaining similar affinities and potencies. Specifically, we introduced aromatic and piperazine moieties in the linker to explore their effect. Overall, similar activities at D2 receptors as observed in our earlier study was maintained in the new molecules e.g. (6S,6'S)-6,6'-((1,4-phenylenebis(ethane-2,1-diyl))bis(propylazanediyl))bis(5,6,7,8-tetrahydronaphthalen-1-ol) (D-382) (Ki, D2 = 3.88 nM). The aromatic moiety in D-382 was next functionalized by introducing hydroxyl groups to mimic polyhydroxy natural products which are known to interact with amyloidogenic proteins. Such a transformation resulted in development of compounds like 2,5-bis(2-(((S)-5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)ethyl)benzene-1,4-diol (D-666) (Ki, D2 = 7.62 nM) which retained similar affinity and potency at D2 receptors. Such dihydroxyl compounds turned out to be potent inhibitors against aggregation and toxicity of recombinant alpha synuclein protein. The work reported here is in line with our overall goal to develop multifunctional dopamine agonist for symptomatic and disease modifying treatment of Parkinson's disease.

Ergonomic and psychosocial risk factors for low back pain among rice farmers in West Bengal, India.

BACKGROUND: Rice farming is considered the most crucial industry in India, where millions of farmers suffer from LBP. OBJECTIVES: The present study's primary objectives were to evaluate the prevalence of low back pain among India's rice farmers and determine the relationship between low back pain and ergonomic risk factors and psychosocial factors encountered by the farmers. METHODS: Socio-demographics, ergonomics risk factors and psychosocial factors that cause LBP among rice farmers were examined. Modified Nordic Musculoskeletal Questionnaire and Oswestry LBP Questionnaire were administered among the farmers to evaluate the LBP. Univariate analysis was done to find out the odds ratios and 95% confidence intervals among the farmers. RESULTS: The primary findings from this study regarding the psychosocial factors, such as perceived inadequacy of income (84.7%), job demands (78.1%), work demand targets specific productivity (76.5%), rigidity in work methods (75.3%), monotony at work (73.2 %), have a relationship with LBP. The results also revealed that the relationship between the low back pain and ergonomic risk factors, such as repetitiveness (OR- 4.215; 95% CI- 2.551-6.965), working in awkward posture (OR- 85.82; 95% CI- 43.134-170.77), lifting loads (OR- 0.281; 95% CI- 0.125-0.324), pulling loads (OR- 0.274; 95% CI- 0.173-0.434), showed significant relationship with LBP in the univariate analysis. CONCLUSIONS: The prevalence of LBP among rice farmers connected with ergonomic and psychosocial risk factors. The awkward posture, MMH (lifting and carrying) are the main causative factors of LBP.

The effects of using an ergonomic aid on the physical workload and body discomfort reported by pre-adolescent farmers in West Bengal, India.

BACKGROUND: Musculoskeletal disorders are one of the major health hazards among farmers. Pre-adolescents are mainly associated with agricultural work due to poor socioeconomic conditions. OBJECTIVES: This study aims to implement a new ergonomics aid for the betterment of job procedures and improvement of productivity, health, and safety of the preadolescent farmers. METHODS: 100 male and 100 female preadolescent farmers were randomly selected from the villages of Tarakeswar, West Bengal, India, to evaluate and reduce work-related musculoskeletal disorders, physiological stress. Modified Nordic questionnaires, Body Part Discomfort (BPD) scale, and handgrip strength were assessed before and after using the ergonomics aid. RESULTS: The results of the study show that there was a significant change (decrease) in discomfort in the lower back, wrists, shoulder, and hands among preadolescent farmers when using the newly designed ergonomic aid. Handgrip strength increased and physiological stress was decreased among preadolescent farmers in post-intervention than pre-intervention in just after work conditions. Productivity has been increased in farming by decreasing absenteeism from work with the use of ergonomic aid. CONCLUSION: This study concludes that productivity has been increased in farming by decreasing absenteeism from work as well as by using the ergonomic aid the discomfort feeling has been decreased markedly.

Assessment of ergonomic exposure, work-related occupational injuries, and prevention: Child work in the brickfield industry in India.

Child labor is an infraction of fundamental human rights, and it prevents the children's physical, psychosocial, and psychological development. In India, children have been working in different unorganized sectors as paid laborers. Children were found performing a fair amount of manual, rigorous tasks in the brickfield industry due to socioeconomic disadvantages. Child brickfield workers suffered from musculoskeletal pain and injuries due to working with a heavy physical workload, which hampers the overall quality of life. A study had been conducted among these child brickfield laborers from India during 2011-2017. The study found laceration (38.7% male and 36.9% female) as the primary injury followed by sprain and strain, scratches, avulsion, and fractures among child brickfield workers. The study shows that child workers are highly prone to injuries, mainly toe (23.9% male and 28.1% female), hands (22.0% male and 23.4% female), wrists, feet, ankles, and fingers. The injury rate among male and female child brickfield laborers was 7.64 and 9.52 per 1000 workers. The primary source of injuries in brickfields was due to falling from height. Several risk factors, including biomechanical, work stress, may play a key role in work-related injuries among child brickfield laborers.

Work-related injuries, postural stress, and musculoskeletal disorders among the railway track maintainers in India.

The main aim of this cross-sectional study was to evaluate work-related injuries (WRI) and the self-reported musculoskeletal symptoms among 742 railway track maintainers. The second aim of this study was to investigate the potential factors related to the prevalence of musculoskeletal disorders (MSDs) in track maintainers. This study also tried to do planning and implementing ergonomic intervention programs to improve track maintainer's health. Modified Nordic questionnaires were administered to assess the prevalence of MSDs. Detailed posture analysis by rapid entire body assessment (REBA) method was performed to assess the risk level of concerned postures. The injury data for 12 months were collected by conducting a survey and personal interviews with the affected railway track maintainers. To assess the prevalence of MSDs, the odds ratio and 95% confidence interval were computed along with critical χ 2 values. Analysis of variance was performed to determine significant differences between the MSD present and absent among the track maintainers of the Indian railway. The result of this study showed that neglect of safety precautions is the main reason for injury, followed by slipping and falling and lack of awareness. Sprain injury is one of the main injuries, followed by cut, snakebite, abrasion, and fracture. Low educational levels of workers are also reasons for WRI. In conclusion, the prevalence and severity of MSD, particularly in the low back, knees, wrist, and shoulder and WRI were found to be very high among the track maintainers. The recommendations of this research are ergonomic interventions, such as track maintainers proper training, following the National Institute of Occupational Safety and Health -recommended weight limit for manual material handling, modification in hand tools, job rotation, performing stretching exercise, and avoiding awkward and static posture are needed.

D-578, an orally active triple monoamine reuptake inhibitor, displays antidepressant and anti-PTSD like effects in rats.

Significant unmet needs exist for development of better pharmacotherapeutic agents for major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) as the current drugs are inadequate. Our goal in this study is to investigate behavioral pharmacological characterization of a novel triple reuptake inhibitor (TRI) D-578 which exhibits nanomolar potency at all three monoamine transporters (Ki; 16.2. 16.2, 3.23 nM, and 29.6, 20.6, 6.10 nM for the rat brain and cloned human dopamine, serotonin and norepinephrine transporters, respectively) and exhibited little to no affinity for other off-target CNS receptors. In a rat forced swim test, compound D-578 upon oral administration displayed high efficacy and not stimulating in locomotor behavior. The effects of D-578 and paroxetine were next evaluated in a rat model for traumatic stress exposure - the single prolonged stress (SPS) model - which has been shown to have construct, predictive, and behavioral validity in modeling aspects of PTSD. Our results show that SPS had no effect on the acquisition of conditioned fear, but impaired extinction learning and extinction retention of fear behavior compared to sham treatment. D-578, but not paroxetine, attenuated the extinction and extinction-retention deficit induced by SPS. These findings suggest that D-578 has greater efficacy in normalizing traumatic stress-induced extinction-retention learning in a model for PTSD compared to paroxetine. Overall these results suggest that D-578, in addition to producing a robust and efficacious antidepressant effect, may attenuate maladaptive retention of fearful memories and support further testing of this agent for the pharmacotherapy of depression and PTSD.

Gender differences in prevalence of musculoskeletal disorders and physiological stress among the brick field workers of West Bengal, India.

BACKGROUND: The manual brick field industry is one of the most important and oldest industries in India, where millions of male and female workers make their livelihood. OBJECTIVE: To estimate the different ergonomic risk factors associated with brick making, identify potential gender differences and the prevalence of Work-related musculoskeletal disorders (WMSDs), physiological and psychological stress among the brickfield workers. METHODS: Brickfield workers - 152 male and 148 female were randomly selected from the 12 brickfields. The Modified Nordic Questionnaire was applied to assess the discomfort reported among both groups of brickfield workers. Objective measurement of physiological parameters and lung function values were also recorded. RESULTS: From this study, it was revealed that there is significantly higher discomfort reported in hands, lower back and knees among female brick molders than male brick molders. The physiological parameters did not show any significant change between male brickfield workers and female brickfield workers. The mean values of FVC, FEV1 and PEFR for females were lower than those for male brickfield workers. CONCLUSION: This study concludes that female brickfield workers reported more discomfort than male brickfield workers; perhaps in part due to their additional domestic work responsibilities.

Design, Synthesis, and Pharmacological Characterization of Carbazole Based Dopamine Agonists as Potential Symptomatic and Neuroprotective Therapeutic Agents for Parkinson's Disease.

We have developed a series of carbazole-derived compounds based on our hybrid D2/D3 agonist template to design multifunctional compounds for the symptomatic and disease-modifying treatment of Parkinson's disease (PD). The lead molecules (-)-11b (D-636), (-)-15a (D-653), and (-)-15c (D-656) exhibited high affinity for both D2 and D3 receptors and in GTPγS functional assay, the compounds showed potent agonist activity at both D2 and D3 receptors (EC50 (GTPγS); D2 = 48.7 nM, D3 = 0.96 nM for 11b, D2 = 0.87 nM, D3 = 0.23 nM for 15a and D2 = 2.29 nM, D3 = 0.22 nM for 15c). In an animal model of PD, the test compounds exhibited potent in vivo activity in reversing hypolocomotion in reserpinized rats with a long duration of action compared to the reference drug ropinirole. In a cellular antioxidant assay, compounds (-)-11b, (-)-15a, and (-)-15c exhibited potent activity in reducing oxidative stress induced by neurotoxin 6-hydroxydopamine (6-OHDA). Also, in a cell-based PD neuroprotection model, these lead compounds significantly increased cell survival from toxicity of 6-OHDA, thereby producing a neuroprotective effect. Additionally, compounds (-)-11b and (-)-15a inhibited aggregation and reduced toxicity of recombinant alpha synuclein protein in a cell based in vitro assay. These observations suggest that the lead carbazole-based dopamine agonists may be promising multifunctional molecules for a viable symptomatic and disease-modifying therapy of PD and should be further investigated.

Health hazards and risks for musculoskeletal problems among child labourers in the brickfield sector of West Bengal, India.

AIMS: The purpose of this study was to describe the health hazards among child labourers in brickfields, and to assess occupational health problems, together with physiological and respiratory stress, compared with child control subjects. METHODS: A cross-sectional study was conducted on 112 child brickfield workers and 120 control subjects, and a modified Nordic Questionnaire was applied to assess the discomfort felt among both groups of workers. Physiological assessment of the workload was carried out by the measurement of heart rate, blood pressure and spirometry of the workers. RESULTS: Child brickfield workers suffer from pain, especially in the lower back (97%), shoulder (88%), hands (82%), wrist (76%), neck (73%) and ankle (71%). The post-activity heart rate of the child brickfield workers was 166.5 beats/min, whereas the systolic and diastolic blood pressures were 132.2 and 67.2 mm/Hg, respectively. The forced vital capacity value of child brickfield workers was 2.04, and in the case of the controls it was 2.18, which was significantly different. The forced expiratory volumes in 1 s of experimental and control subjects were 1.82 and 1.92, respectively. The peak expiratory flow rate was significantly different between the two groups. CONCLUSIONS: Most of the brick-making activities were strenuous ones that affected the children. The cardiovascular and respiratory health of the child brickfield workers has changed markedly due to strenuous activity. The child brickfield workers also experienced other occupational health problems and severe musculoskeletal pain.

Occupational agricultural injuries among the preadolescent workers of West Bengal, India.

INTRODUCTION: Agricultural injuries are an important factor in mortality and morbidity for populations of preadolescents globally. Working preadolescents in agricultural sector are exposed to occupational risks and injury in India. OBJECTIVE: This study mainly assesses the nature of injuries among the preadolescent agricultural workers of West Bengal, India. METHODS: The survey was done by collecting the data on agricultural injuries from the Hooghly district of West Bengal. The injury data for 7 years between years 2010 and 2016 were collected by conducting a survey and personal interviews with the victims. The questionnaire-based approach was used for data collection information on the injury characteristics. RESULTS: The agricultural injury incident rate was 8.99 (male) and 7.89 (female) per 1000 workers/year. The leading causes of farm injuries were hand tools (65.7%). The most frequently involved tools were spades and sickles. The main cause of hand tool injuries was repetitive work, which lead to fatigue and slippage of hand tools from the hand. The study indicated that preadolescent workers are highly prone to injuries in their occupation, mostly affecting the toes (27.8% and 26.3%) and fingers (24.8% and 25%) in both male and female preadolescents, which consequently affected their health, productivity and work performance. CONCLUSION: This study concludes that (1) agricultural injuries affecting different body parts such as toes, fingers, feet and ankles. (2) Occurrence of injuries was much higher among males than females. (3) Hand tools accounted for the majority of injuries followed by farm machinery. (4) Cut injuries are the main ones followed by lacerations, abrasions, sprains and contusions.

D-512, a novel dopamine D2/3 receptor agonist, demonstrates greater anti-Parkinsonian efficacy than ropinirole in Parkinsonian rats.

BACKGROUND AND PURPOSE: Symptoms of Parkinson's disease are commonly managed using selective dopamine D2/3 receptor agonists, including ropinirole. While D2/3 agonists are useful in early-stage Parkinson's disease, they tend to lose efficacy in later disease stages and do not appear to modify disease progression. We have recently developed a novel 'multifunctional' compound, D-512: a high-affinity D2/3 receptor agonist with antioxidant and other neuroprotective properties that may limit Parkinson's disease progression. This study sought to compare the anti-Parkinsonian properties of the clinically used compound, ropinirole, with those of the novel compound, D-512. EXPERIMENTAL APPROACH: A rat model of Parkinson's disease was created by unilaterally infusing 6-hydroxydopamine, a dopamine neurotoxin, into the medial forebrain bundle. D-512 was compared with ropinirole for ability to stimulate spontaneous motor activity and reverse Parkinsonian akinesia. These beneficial effects were compared against each drug's liability to provoke dyskinesia, a common motor side effect. KEY RESULTS: Both compounds increased spontaneous movement, but D-512 showed a longer duration of action. Only D-512 was able to significantly reverse forelimb akinesia. Drug-induced dyskinesia was similar for equivalent doses. CONCLUSIONS AND IMPLICATIONS: Compared with ropinirole, D-512 showed greater peak-dose efficacy and a longer duration of action, despite a similar side-effect profile. Our results add to earlier data showing that D-512 is superior to available D2/3 agonists and could merit clinical investigation.

A novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-syn- and MPTP-induced toxicities in vivo.

Here, we report the characterization of a novel hybrid D2/D3 agonist and iron (II) specific chelator, D-607, as a multi-target-directed ligand against Parkinson's disease (PD). In our previously published report, we showed that D-607 is a potent agonist of dopamine (DA) D2/D3 receptors, exhibits efficacy in a reserpinized PD animal model and preferentially chelates to iron (II). As further evidence of its potential as a neuroprotective agent in PD, the present study reveals D-607 to be protective in neuronal PC12 cells against 6-OHDA toxicity. In an in vivo Drosophila melanogaster model expressing a disease-causing variant of α-synuclein (α-Syn) protein in fly eyes, the compound was found to significantly suppress toxicity compared to controls, concomitant with reduced levels of aggregated α-Syn. Furthermore, D-607 was able to rescue DAergic neurons from MPTP toxicity in mice, a well-known PD neurotoxicity model, following both sub-chronic and chronic MPTP administration. Mechanistic studies indicated that possible protection of mitochondria, up-regulation of hypoxia-inducible factor, reduction in formation of α-Syn aggregates and antioxidant activity may underlie the observed neuroprotection effects. These observations strongly suggest that D-607 has potential as a promising multifunctional lead molecule for viable symptomatic and disease-modifying therapy for PD.

A Novel Iron(II) Preferring Dopamine Agonist Chelator as Potential Symptomatic and Neuroprotective Therapeutic Agent for Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, and development of disease-modifying treatment is still an unmet medical need. Considering the implication of free iron(II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-)-12 (D-607) as a multitarget-directed ligand against PD. Binding and functional assays at dopamine D2/D3 receptors indicate potent agonist activity of (-)-12. The molecule displayed an efficient preferential iron(II) chelation properties along with potent in vivo activity in a reserpinized PD animal model. The compound also rescued PC12 cells from toxicity induced by iron delivered intracellularly in a dose-dependent manner. However, Fe3+ selective dopamine agonist 1 and a well-known antiparkinsonian drug pramipexole produced little to no neuroprotection effect under the same experimental condition. These observations strongly suggest that (-)-12 should be a promising multifunctional lead molecule for a viable symptomatic and disease modifying therapy of PD.

Assessment of respiratory symptoms and lung function values among the brick field workers of West Bengal, India.

Brick manufacturing process releases large amounts of silica dust into the work environment due to the use of silica-containing materials. The main aim of the study was to investigate the impairment of lung function and prevalence of respiratory symptoms among the different groups of brick field workers in comparison with control subjects. A total of 250 brick field workers and 130 unexposed control subjects were randomly selected in which demographic characteristics, respiratory symptoms, and lung function values were recorded. The result showed significantly lower p value (<.001) in lung function and respiratory symptoms among brick field workers when compared with control group. The prevalence of respiratory symptoms was dyspnea (46.8%), phlegm (39.2%), and chest tightness (27.6%). Dust exposure in working environment affected the lung function values and increased the respiratory symptoms among the brick field workers.