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1.  Longitudinal assessment of chlorpyrifos exposure and self-reported neurological symptoms in adolescent pesticide applicators 
BMJ Open  2014;4(3):e004177.
Objectives
Occupational exposure of organophosphorus pesticides, such as chlorpyrifos (CPF), in adolescents is of particular concern because of the potential vulnerability of the developing neurological system. The objectives of this study were to examine how neurological symptoms reported over the application season vary across time, whether these effects are reversible postapplication and if there are associations between CPF biomarkers and neurological symptoms in an adolescent study population.
Setting
The longitudinal study was conducted in two agricultural districts of Menoufia Governorate, Egypt between April 2010 and January 2011.
Participants
Male adolescent participants, including CPF applicators (n=57) and non-applicators (n=38), were recruited.
Primary and secondary outcome measures
Self-reported data for 25 neurological symptoms were collected at 32 time points over the 8-month period before, during and after the application season. Additionally, urine and blood samples were collected to measure urine trichloro-2-pyridinol (TCPy), a CPF-specific biomarker and blood cholinesterase activity.
Results
Applicators and non-applicators report the highest numbers of symptoms during the application season, followed by a reduction in symptoms after the application ended. Applicators reported a greater percentage of neurological symptoms, relative to baseline, than non-applicators after accounting for potential covariates. Among the applicators, cumulative TCPy was positively and significantly associated with the average percentage of symptoms (B=4.56, 95% CI 3.29 to 5.84; p<0.001). Significant associations (p=0.03–0.07) between the change in butyrylcholinesterase activity from the preapplication to the postapplication season and several domains of neurological symptoms were also found, even after adjusting for potential covariates.
Conclusions
These observations demonstrate changes in the reporting of symptoms across the application season, showing an increase in symptom reporting during application and recovery following the end of pesticide application. These findings reinforce the growing concern regarding the neurotoxic health effects of CPF in adolescent applicators in developing countries and the need for developing and implementing intervention programmes.
doi:10.1136/bmjopen-2013-004177
PMCID: PMC3948636  PMID: 24595133
2.  Longitudinal Assessment of Chlorpyrifos Exposure and Effect Biomarkers in Adolescent Egyptian Agricultural Workers 
Chlorpyrifos (CPF) is applied seasonally in Egypt by adolescent agricultural workers and the extent of occupational exposure and the potential for environmental CPF exposure in this population is poorly understood. Adolescent pesticide applicators (n=57; 12–21 years of age) and age matched non-applicators (n=38) from the same villages were followed for 10 months in 2010, spanning pre-application through post-application. Eight urine and 5 blood samples were collected from participants within this time period. Blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (exposure/effect biomarker) and urine 3,5,6-trichloro-2-pyridinol (TCPy) (exposure biomarker) were used to assess occupational CPF exposures in pesticide applicators and environmental exposures in non-applicators. Applicators demonstrated significantly higher TCPy concentration and BChE depression than non-applicators throughout CPF application. This difference persisted for 4–7 weeks after the cessation of agricultural spraying. However, both groups exhibited significantly elevated TCPy and depressed BChE, compared to their respective baseline. The peak TCPy levels during the spray season (95% confidence interval) for non-applicators and applicators reached 16.8 (9.87–28.5) and 137 (57.4–329) ug/g creatinine, respectively. BChE levels (95% confidence intervals) during the spray were 1.47 (1.28–1.68) for non-applicators and 0.47 (0.24–0.94) U/ml for applicators. The longitudinal assessment of CPF biomarkers provided robust measures of exposure and effect throughout CPF application in adolescents and revealed significant exposures in both applicators and non-applicators. Biomarker data in the non-applicators, which mirrored that of the applicators, indicated that non-applicators received environmental CPF exposures. This suggests that similar exposures may occur in other residents of this region during periods of pesticide application.
doi:10.1038/jes.2012.113
PMCID: PMC3926695  PMID: 23321857
chlorpyrifos; acetylcholinesterase; butyrylcholinesterase; TCPy; occupational exposure; environmental exposure
3.  Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial 
Lancet  2013;382(9903):1496-1506.
Summary
Background
Fetal lower urinary tract obstruction (LUTO) is associated with high perinatal and long-term childhood mortality and morbidity. We aimed to assess the effectiveness of vesicoamniotic shunting for treatment of LUTO.
Methods
In a randomised trial in the UK, Ireland, and the Netherlands, women whose pregnancies with a male fetus were complicated by isolated LUTO were randomly assigned by a central telephone and web-based randomisation service to receive either the intervention (placement of vesicoamniotic shunt) or conservative management. Allocation could not be masked from clinicians or participants because of the invasive nature of the intervention. Diagnosis was by prenatal ultrasound. The primary outcome was survival of the baby to 28 days postnatally. All primary analyses were done on an intention-to-treat basis, but these results were compared with those of an as-treated analysis to investigate the effect of a fairly large proportion of crossovers. We used Bayesian methods to estimate the posterior probability distribution of the effectiveness of vesicoamniotic shunting at 28 days. The study is registered with the ISRCTN Register, number ISRCTN53328556.
Findings
31 women with singleton pregnancies complicated by LUTO were included in the trial and main analysis, with 16 allocated to the vesicoamniotic shunt group and 15 to the conservative management group. The study closed early because of poor recruitment. There were 12 livebirths in each group. In the vesicoamniotic shunt group one intrauterine death occurred and three pregnancies were terminated. In the conservative management group one intrauterine death occurred and two pregnancies were terminated. Of the 16 pregnancies randomly assigned to vesicoamniotic shunting, eight neonates survived to 28 days, compared with four from the 15 pregnancies assigned to conservative management (intention-to-treat relative risk [RR] 1·88, 95% CI 0·71–4·96; p=0·27). Analysis based on treatment received showed a larger effect (3·20, 1·06–9·62; p=0·03). All 12 deaths were caused by pulmonary hypoplasia in the early neonatal period. Sensitivity analysis in which non-treatment-related terminations of pregnancy were excluded made some slight changes to point estimates only. Bayesian analysis in which the trial data were combined with elicited priors from experts suggested an 86% probability that vesicoamniotic shunting increased survival at 28 days and a 25% probability that it had a large, clinically important effect (defined as a relative increase of 55% or more in the proportion of neonates who survived). There was substantial short-term and long-term morbidity in both groups, including poor renal function—only two babies (both in the shunt group) survived to 2 years with normal renal function. Seven complications occurred in six fetuses from the shunt group, including spontaneous ruptured membranes, shunt blockage, and dislodgement. These complications resulted in four pregnancy losses.
Interpretation
Survival seemed to be higher in the fetuses receiving vesicoamniotic shunting, but the size and direction of the effect remained uncertain, such that benefit could not be conclusively proven. Our results suggest that the chance of newborn babies surviving with normal renal function is very low irrespective of whether or not vesicoamniotic shunting is done.
Funding
UK National Institute of Health Research, Wellbeing of Women, Hannah Eliza Guy Charity (Birmingham Children's Hospital Charity).
doi:10.1016/S0140-6736(13)60992-7
PMCID: PMC3898962  PMID: 23953766
4.  Identification of etiological agents by LPA and PCR in childhood meningitis 
Pakistan Journal of Medical Sciences  2013;29(5):1162-1166.
Objectives: To determine the etiological agents by Latex Particle Agglutination (LPA) and Polymerase Chain Reaction (PCR) in patients admitted with Cerebrospinal Fluid (CSF) culture negative bacterial meningitis
Methods: This descriptive case series was conducted at National Institute of Child Health, Karachi from January 2010 to December 2012. Patients meeting the WHO case definition of suspected meningitis from one month to 59 months of age were included in the study. CSF examination and culture was carried out on every patient and CSF culture negative patients were enrolled. Demographic data, clinical signs & symptoms and laboratory findings were entered into the proforma. Data was analyzed using statistical package for social sciences (SPSS) version 17. P-value <0.05 was taken as significant.
Results: A total of 166 patients were included. Male were 96 and female were 76 with the male to female ratio of 1.26. The mean age of patient was ± SD 14.6 ± 14.5 months. The etiological agents identified by LPA were in 26/166 (15.66%) cases and the organisms were H. influenzae type b 10 cases, streptococcus pneumoniae 15 cases and meningococcus only one case respectively. The organisms identified by PCR were in 65/166 (39.15%) cases and the isolates were H. influenzae type b 16 cases, streptococcus pneumoniae 48 cases and meningococcus 01 case respectively.
Conclusion: LPA and PCR are superior and useful diagnostic tools in microbiology. They can be used for rapid etiological diagnosis of bacterial meningitis for the early administration of proper antibiotic.
Abbreviation: LPA = Latex Particle Agglutination, PCR = Polymerase Chain Reaction, CSF = Cerebrospinal Fluid, CNS = Central Nervous System.
PMCID: PMC3858925  PMID: 24353712
Etiological Agents; Meningitis
5.  On-the-Job Evidence-Based Medicine Training for Clinician-Scientists of the Next Generation 
The Clinical Biochemist Reviews  2013;34(2):93-103.
Clinical scientists are at the unique interface between laboratory science and frontline clinical practice for supporting clinical partnerships for evidence-based practice. In an era of molecular diagnostics and personalised medicine, evidence-based laboratory practice (EBLP) is also crucial in aiding clinical scientists to keep up-to-date with this expanding knowledge base. However, there are recognised barriers to the implementation of EBLP and its training. The aim of this review is to provide a practical summary of potential strategies for training clinician-scientists of the next generation.
Current evidence suggests that clinically integrated evidence-based medicine (EBM) training is effective. Tailored e-learning EBM packages and evidence-based journal clubs have been shown to improve knowledge and skills of EBM. Moreover, e-learning is no longer restricted to computer-assisted learning packages. For example, social media platforms such as Twitter have been used to complement existing journal clubs and provide additional post-publication appraisal information for journals.
In addition, the delivery of an EBLP curriculum has influence on its success. Although e-learning of EBM skills is effective, having EBM trained teachers available locally promotes the implementation of EBM training. Training courses, such as Training the Trainers, are now available to help trainers identify and make use of EBM training opportunities in clinical practice. On the other hand, peer-assisted learning and trainee-led support networks can strengthen self-directed learning of EBM and research participation among clinical scientists in training. Finally, we emphasise the need to evaluate any EBLP training programme using validated assessment tools to help identify the most crucial ingredients of effective EBLP training.
In summary, we recommend on-the-job training of EBM with additional focus on overcoming barriers to its implementation. In addition, future studies evaluating the effectiveness of EBM training should use validated outcome tools, endeavour to achieve adequate power and consider the effects of EBM training on learning environment and patient outcomes.
PMCID: PMC3799223  PMID: 24151345
7.  Benzimidazole, coumrindione and flavone derivatives as alternate UV laser desorption ionization (LDI) matrices for peptides analysis 
Background
Matrix-assisted laser desorption/ionization (MALDI) is a soft ionization mass spectrometric technique, allowing the analysis of bio-molecules and other macromolecules. The matrix molecules require certain characteristic features to serve in the laser desorption/ionization mechanism. Therefore, only a limited number of compounds have been identified as ultraviolet- laser desorption/ionization (UV-LDI) matrices. However, many of these routine matrices generate background signals that useful information is often lost in them. We have reported flavones, coumarindione and benzimidazole derivatives as alternate UV-LDI matrices.
Results
Thirty one compounds have been successfully employed by us as matrices for the analysis of low molecular weight (LMW) peptides (up to 2000 Da). Two peptides, bradykinin and renin substrate tetra-decapeptide were analyzed by using the newly developed matrices. The MS measurements were made after mixing the matrix solution with analyte by using dried droplet sample preparation procedures. The synthesized matrix materials showed better S/N ratios and minimal background signals for low mass range. Furthermore, pico molar concentrations of [Glu1]-fibrinopeptide B human could be easily analyzed with these matrices. Finally, BSA-digest was analyzed and identified through database search against Swiss-Prot by using Mascot.
Conclusions
These results validate the good performance of the synthesized UV-laser desorption/ionization (LDI) matrices for the analysis of low molecular weight peptides.
doi:10.1186/1752-153X-7-77
PMCID: PMC3680071  PMID: 23621998
MALDI-MS; LDI matrix; Benzimidazole derivatives; Coumarin derivatives; Flavones; Peptides
8.  1-(2-Methyl-5-nitro-1H-imidazol-1-yl)acetone 
In the mol­ecule of the title compound, C7H9N3O3, the nitro and carbonyl groups are tilted with respect to the imidazole ring by 9.16 (6) and 65.47 (7)°, respectively. Neighbouring chains are linked via C—H⋯N and C—H⋯O hydrogen bonds forming two-dimensional slab-like networks lying parallel to (01-1).
doi:10.1107/S1600536813006569
PMCID: PMC3629604  PMID: 23634091
9.  Dysmenorrhoea 
Clinical Evidence  2011;2011:0813.
Introduction
Dysmenorrhoea may begin soon after the menarche, after which it often improves with age, or it may originate later in life after the onset of an underlying causative condition. Dysmenorrhoea is common, and in up to 20% of women it may be severe enough to interfere with daily activities.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for primary dysmenorrhoea? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 35 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupressure, acupuncture, aspirin, behavioural interventions, contraceptives (combined oral), fish oil, herbal remedies, magnets, non-steroidal anti-inflammatory drugs, paracetamol, progestogens (intrauterine), spinal manipulation, surgical interruption of pelvic nerve pathways, thiamine, toki-shakuyaku-san, topical heat, transcutaneous electrical nerve stimulation (TENS), vitamin B12, and vitamin E.
Key Points
Dysmenorrhoea may begin soon after the menarche, where it often improves with age, or may originate later in life after the onset of an underlying causative condition. Dysmenorrhoea is very common, and in up to 20% of women it may be severe enough to interfere with daily activities.Dysmenorrhoea is more likely in women who smoke, and those with an earlier age at menarche or longer duration of menstruation.
NSAIDs reduce moderate to severe pain in women with primary dysmenorrhoea compared with placebo, but we don't know whether any one NSAID is superior to the others. Simple analgesics such as aspirin and paracetamol may reduce pain in the short term, although few studies have been of good quality.The herbal remedies toki-shakuyaku-san and Iranian herbal remedy (saffron, celery, and anise) may reduce pain compared with placebo. We don't know whether Chinese herbal remedies are beneficial compared with placebo, but we found limited evidence that they may be effective compared with other treatments for dysmenorrhoea. Thiamine and vitamin E may reduce pain compared with placebo in young women with primary dysmenorrhoea.
Combined oral contraceptives may be more effective at reducing pain in women with primary dysmenorrhoea compared with placebo; however, few trials have been of good quality.
Topical heat (about 39 °C) may be as effective as ibuprofen and more effective than paracetamol at reducing pain. High-frequency transcutaneous electrical nerve stimulation (TENS) may reduce pain compared with sham TENS, but seems to be less effective than ibuprofen. Acupressure may be more effective than sham acupressure or no treatment at relieving dysmenorrhoea. Spinal manipulation may be no more effective than placebo at reducing pain after 1 month in women with primary dysmenorrhoea. Relaxation may be better than no treatment at relieving dysmenorrhoea.We don't know whether acupuncture, fish oil, vitamin B12 , magnets, or intrauterine progestogens reduce dysmenorrhoea. Surgical interruption of pelvic nerve pathways is not beneficial in treating dysmenorrhoea, and may be associated with adverse effects including constipation.
PMCID: PMC3275141  PMID: 21718556
10.  (E)-2,4-Dimethyl-N′-(2-methyl­benzyl­idene)benzohydrazide 
In the title benzoyl­hydrazide derivative, C17H18N2O, the dihedral angle between the benzene rings is 88.45 (8)° and the azomethine double bond adopts an E conformation. In the crystal, mol­ecules are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming a chain along the b axis.
doi:10.1107/S1600536813004388
PMCID: PMC3588470  PMID: 23476582
11.  5-Chloro-2-(4-meth­oxy­phen­yl)-1,3-benzo­thia­zole 
In the title compound, C14H10ClNOS, the dihedral angle between the benzothia­zole ring system and the meth­oxy-substituted benzene ring is 8.76 (16)°. In the crystal, mol­ecules are stacked in columns along the c axis and no significant inter­molecular inter­actions are observed.
doi:10.1107/S1600536813001955
PMCID: PMC3588450  PMID: 23476550
12.  Manganese Exposure from Drinking Water and Children’s Academic Achievement 
Neurotoxicology  2011;33(1):91-97.
Drinking water manganese (WMn) is a potential threat to children’s health due to its associations with a wide range of outcomes including cognitive, behavioral and neuropsychological effects. Although adverse effects of Mn on cognitive function of the children indicate possible impact on their academic achievement little evidence on this issue is available.. Moreover, little is known regarding potential interactions between exposure to Mn and other metals, especially water arsenic (WAs). In Araihazar, a rural area of Bangladesh, we conducted a cross-sectional study of 840 children to investigate associations between WMn and WAs and academic achievement in mathematics and languages among elementary school-children, aged 8–11 years. Data on As and Mn exposure were collected from the participants at the baseline of an ongoing longitudinal study of school-based educational intervention. Annual scores of the study children in languages (Bangla and English) and mathematics were obtained from the academic achievement records of the elementary schools. WMn above the WHO standard of 400 μg/L was associated with 6.4 percentage score loss (95% CI=0.5, 12.3) in mathematics achievement test scores, adjusted for WAs and other sociodemographic variables. We did not find any significant associations between WMn and academic achievement in either language. Neither WAs nor urinary As was significantly related to any of the three academic achievement scores. Our finding suggests that a large number of children in rural Bangladesh may experience deficits in mathematics due to high concentrations of Mn exposure in drinking water.
doi:10.1016/j.neuro.2011.12.002
PMCID: PMC3282923  PMID: 22182530
Bangladesh; children; academic achievement; Math score; manganese; water; classroom behavior
13.  2-{[(Dimethyl­amino)­methyl­idene]amino}-5-nitro­benzonitrile 
The title mol­ecule, C10H10N4O2, is almost planar and adopts an E configuration of the azomethine [C=N = 1.298 (2) Å] double bond. The benzene ring is attached to an essentially planar (r.m.s. deviation = 0.0226 Å) amidine moiety (N=CN/Me2), the dihedral angle between the two mean planes being 18.42 (11)°. The cyano group lies in the plane of the benzene ring [the C and N atoms deviating by 0.030 (3) and 0.040 (3) Å, respectively], while the nitro group makes a dihedral angle 5.8 (3)° with the benzene ring. There are two distinct inter­molecular hydrogen bonds, C—H⋯O and C—H⋯N, that stabilize the crystal structure; the former inter­actions result in centrosymmetric dimers about inversion centers resulting in ten-membered rings, while the later give rise to chains of mol­ecules running parallel to the b axis.
doi:10.1107/S1600536812048866
PMCID: PMC3588379  PMID: 23476456
14.  N-(2,5-Dimeth­oxy­phen­yl)-6-nitro­quinazolin-4-amine 
In the title mol­ecule, C16H14N4O4, the quinazoline ring is substanti­ally planar (r.m.s. deviation = 0.0129 Å) and forms a dihedral angle of 2.73 (8)° with the benzene ring. The conformation of the mol­ecule is stabilized by an intra­molecular C—H⋯N hydrogen bond. In the crystal, mol­ecules are linked into chains running parallel to the b axis by C—H⋯O hydrogen bonds. In addition, π–π stacking is observed between dimethoxy-substituted and nitro-substituted benzene rings, with centroid–centroid distances in the range 3.6438 (10)–3.7148 (10) Å.
doi:10.1107/S1600536812048878
PMCID: PMC3588306  PMID: 23476461
15.  N′-(3-Chloro­benzyl­idene)-4-hy­droxy­benzohydrazide 
The mol­ecule of the title compound, C14H11ClN2O2 adopts an E conformation of the azomethine double bond and the dihedral angle between the benzene rings is 38.96 (13)°. In the crystal, mol­ecules are linked by N—H⋯O and O—H⋯O (with the ketone O atom as acceptor) and C—H⋯O (with the hy­droxy O atom as acceptor) hydrogen bonds, forming a three-dimensional network.
doi:10.1107/S1600536812048325
PMCID: PMC3589070  PMID: 23476306
16.  3-(2-Ethyl-2-phenyl­hydrazin-1-yl­idene)indolin-2-one 
In the title compound, C16H15N3O, the dihedral angle between the indole ring system (r.m.s. deviation = 0.020 Å) and the phenyl ring is 14.49 (9)°. The mol­ecular conformation is supported by an intra­molecular C—H⋯O inter­action, which closes an S(7) ring. In the crystal, inversion dimers linked by pairs of N—H⋯O hydrogen bonds generate R 2 2(8) loops.
doi:10.1107/S1600536812047988
PMCID: PMC3589046  PMID: 23476282
17.  5-Chloro-2-(3,4,5-trimeth­oxy­phen­yl)-1,3-benzothia­zole 
In the title compound, C16H14ClNO3S, the dihedral angle between the almost-planar benzothia­zole ring system [maximum deviation = 0.012 (3) Å] and the aromatic ring of the trimeth­oxy­phenyl group is 15.56 (6)°. In the crystal, the mol­ecules are arranged into layers parallel to the bc plane, held together only by weak van der Waals forces.
doi:10.1107/S1600536812039372
PMCID: PMC3470404  PMID: 23125817
18.  Ethyl (E)-3-(6-methyl-4-oxo-4H-chromen-3-yl)prop-2-enoate 
In the title compound, C15H14O4, the chromone ring system is close to being planar [maximum deviation = 0.015 (2) Å]. The double bond of the ethyl prop-2-enoate chain adopts an E conformation and an intra­molecular C—H⋯O hydrogen bond generates an S6 ring. In the crystal, inversion dimers linked by pairs of C—H⋯O hydrogen bonds generate R 2 2(14) loops. Weak π–π inter­actions [centroid–centroid distance = 3.8493 (12) Å] also occur.
doi:10.1107/S1600536812038585
PMCID: PMC3470320  PMID: 23125733
19.  6-Methyl-4-oxo-4H-chromene-3-carbaldehyde 
In the title compound, C11H8O3, the benzopyran-4-one or chromone ring system is almost planar, with a maximum deviation of 0.045 (2) Å. The crystal structure is stablized by π–π inter­actions between the benzene and pyran rings of inversion-related mol­ecules stacked along the b axis, with a centroid–centroid distance of 3.5463 (12) Å
doi:10.1107/S1600536812037555
PMCID: PMC3470266  PMID: 23125710
20.  2-(5-Chloro-1,3-benzothia­zol-2-yl)-4-meth­oxy­phenol 
In the mol­ecule of the title compound, C14H10ClNO2S, the dihedral angle between the almost planar benzothia­zole ring system [maximum deviation = 0.005 (2) Å] and the benzene ring is 1.23 (9)°. The conformation of the mol­ecule is stabilized by an intra­molecular O—H⋯N hydrogen bond, forming an S(6) ring motif. In the crystal, mol­ecules are linked into layers parallel to the ac plane by C—H⋯O hydrogen bonds and π–π stacking inter­actions [centroid–centroid distance = 3.7365 (12) Å].
doi:10.1107/S1600536812037804
PMCID: PMC3470231  PMID: 23125675
21.  5-Chloro-2-phenyl-1,3-benzothia­zole 
In the structure of the title compound, C13H8ClNS, the dihedral angle between the benzothia­zole ring system and the phenyl ring is 7.11 (8)°. In the crystal, mol­ecules are arranged parallel to the c axis.
doi:10.1107/S1600536812036057
PMCID: PMC3435826  PMID: 22969672
22.  1-(3-Meth­oxy­phen­yl)-2-(phenyl­sulfon­yl)ethan-1-one 
In the title compound, C15H14O4S, the dihedral angle between the benzene and phenyl rings is 88.74 (10)°. In the crystal, mol­ecules are linked into a three-dimensional network by C—H⋯O hydrogen bonds and π–π stacking inter­actions [centroid–centroid distances = 3.6092 (13)–3.8651 (13) Å].
doi:10.1107/S1600536812032795
PMCID: PMC3415004  PMID: 22904991
23.  The Emergence and Maintenance of Vector-Borne Diseases in the Khyber Pakhtunkhwa Province, and the Federally Administered Tribal Areas of Pakistan 
Human populations throughout much of the world are experiencing unprecedented changes in their relationship to the environment and their interactions with the animals with which so many humans are intimately dependent upon. These changes result not only from human induced changes in the climate, but also from population demographic changes due to wars, social unrest, behavioral changes resulting from cultural mixing, and large changes in land-use practices. Each of these social shifts can affect the maintenance and emergence of arthropod vectors disease or the pathogenic organisms themselves. A good example is the country of Pakistan, with a large rural population and developing urban economy, it also maintains a wide diversity of entomological disease vectors, including biting flies, mosquitoes, and ticks. Pathogens endemic to the region include the agents of piroplasmosis, rickettsiosis, spirochetosis, and viral hemorrhagic fevers and encephalitis. The northwestern region of the country, including the Khyber Pakhtunkhwa Province (KPK), formerly the North-West Frontier Provence (NWFP), and the Federally Administered Tribal Areas (FATA) are mountainous regions with a high degree of habitat diversity that has recently undergone a massive increase in human population density due to an immigrating refugee population from neighboring war-torn Afghanistan. Vector-borne diseases in people and livestock are common in KPK and FATA regions due to the limited use of vector control measures and access to livestock vaccines. The vast majority of people in this region live in abject poverty with >70% of the population living directly from production gained in animal husbandry. In many instances whole families live directly alongside their animal counterparts. In addition, there is little to no awareness of the threat posed by ticks and transmission of either zoonotic or veterinary pathogens. Recent emergence of Crimean–Congo hemorrhagic fever virus in rural populations, outbreaks of Dengue hemorrhagic fever have been reported in the region, and high prevalence of cattle infected and co-infected with multiple species of hemoparasites (Theileria, Babesia, Anaplasma). The emergence of which has followed the increased density of the rural population due to an influx of refugees from violent conflicts in Afghanistan and is exacerbated by an already impoverished society and wide diversity of potential arthropod vectors. These human outbreaks may be exacerbated by episodes of social upheaval but are also tied to the historically close association of people in the region with their livestock and subsequent zoonosis that result from spillover from co-habitation with infected domestic animals.
doi:10.3389/fphys.2012.00250
PMCID: PMC3429027  PMID: 22934007
Anaplasma; Babesia; Crimean-Congo hemorrhagic fever; dengue virus; Eid Islamic festival; hemoparasites; emerging and re-emerging disease
24.  8-[(2-Hy­droxy­phen­yl)imino]-3,5a,9-trimethyl-3a,4,5,5a,8,9b-hexa­hydro­naphtho­[1,2-b]furan-2(3H)-one 
The title compound, C21H23NO3, is a phenyl­imine derivative of the well known anthelmintic agent α-santonin. The trans-fused cyclo­hexane and γ-lactone rings of the α-santonin ring system adopt chair and envelope conformations, respectively, whereas the hexa­diene ring is approximately planar [maximum deviation = 0.029 (4) Å] and forms a dihedral angle of 62.30 (11)° with the benzene ring. An intra­molecular O—H⋯N hydrogen bond is observed.
doi:10.1107/S1600536812027146
PMCID: PMC3393965  PMID: 22798830
25.  3,5a,9-Trimethyl-8-(2-phenylhydrazin-1-ylidene)-4,5,5a,9b-tetrahydro-3aH,8H-naphtho[1,2-b]furan-2(3H)-one 
The title compound, C21H24N2O2, is a phenyl hydrazine derivative of the well known anthelminthic agent α-santonin, which is composed of three fused rings (benzodieneone, cyclo­hexane and γ-lactone). The cyclo­hexa­dienone ring adopts a boat conformation, the cyclo­hexane ring is in a chair conformation and the trans-fused γ-lactone ring adopts a C-envelope conformation. In the crystal, mol­ecules are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming chains along the a axis.
doi:10.1107/S1600536812023847
PMCID: PMC3393924  PMID: 22798789

Results 1-25 (97)