Creeping mediastinal lymphangioma transgressing anatomical compartments: A rare case in an adult female patient.

Lymphangiomas, also known as lymphatic malformations, are rare non-neoplastic lesions of vascular origin showing lymphatic differentiation. These are most commonly reported in children within the neck and axillary region; however, mediastinum remains the commonest site in adults whereby diagnosis is usually incidental on imaging done for non-specific symptoms. Radiologically, these lesions are well-defined multicystic non-enhancing masses, with CT attenuation values ranging from simple to complex fluid and fat. Being benign, these mostly present clinically either due to mass effect exerted on structures, secondarily infected or developing intra lesion haemorrhage. We present a rare case of mediastinal lymphangioma with secondary hilar and intrapulmonary extension in a middle-aged female presenting with occasional haemoptysis and shortness of breath. The patient underwent thoracotomy with complete dissection of the mediastinal tumour, per operative Bleomycin administration in pulmonary component, and made subsequent uneventful post-operative recovery.

The molecular genetics of human appendicular skeleton.

Disorders that result from de-arrangement of growth, development and/or differentiation of the appendages (limbs and digit) are collectively called as inherited abnormalities of human appendicular skeleton. The bones of appendicular skeleton have central role in locomotion and movement. The different types of appendicular skeletal abnormalities are well described in the report of "Nosology and Classification of Genetic skeletal disorders: 2019 Revision". In the current article, we intend to present the embryology, developmental pathways, disorders and the molecular genetics of the appendicular skeletal malformations. We mainly focused on the polydactyly, syndactyly, brachydactyly, split-hand-foot malformation and clubfoot disorders. To our knowledge, only nine genes of polydactyly, five genes of split-hand-foot malformation, nine genes for syndactyly, eight genes for brachydactyly and only single gene for clubfoot have been identified to be involved in disease pathophysiology. The current molecular genetic data will help life sciences researchers working on the rare skeletal disorders. Moreover, the aim of present systematic review is to gather the published knowledge on molecular genetics of appendicular skeleton, which would help in genetic counseling and molecular diagnosis.

A novel protein truncating mutation in L2HGDH causes L-2-hydroxyglutaric aciduria in a consanguineous Pakistani family.

BACKGROUND: L-2-hydroxyglutaric aciduria (L2HGA) is a rare neurometabolic disorder that occurs due to accumulation of L-2-hydroxyglutaric acid in the cerebrospinal fluid (CSF), plasma and urine. The clinical manifestation of L2HGA includes intellectual disability, cerebellar ataxia, epilepsy, speech problems and macrocephaly. METHODS: In the present study, we ascertained a multigenerational consanguineous Pakistani family with 5 affected individuals. Clinical studies were performed through biochemical tests and brain CT scan. Locus mapping was carried out through genome-wide SNP genotyping, whole exome sequencing and Sanger sequencing. For in silico studies protein structural modeling and docking was done using I-TASSER, Cluspro and AutoDock VINA tools. RESULTS: Affected individuals presented with cognitive impairment, gait disturbance, speech difficulties and psychomotor delay. Radiologic analysis of a male patient revealed leukoaraiosis with hypoattenuation of cerebral white matter, suggestive of hypomyelination. Homozygosity mapping in this family revealed a linkage region on chromosome 14 between markers rs2039791 and rs781354. Subsequent whole exome analysis identified a novel frameshift mutation NM_024884.3:c.180delG, p.(Ala62Profs*24) in the second exon of L2HGDH. Sanger sequencing confirmed segregation of this mutation with the disease phenotype. The identification of the most N-terminal loss of function mutation published thus far further expands the mutational spectrum of L2HGDH.

Alopecia-mental retardation syndrome: Molecular genetics of a rare neuro-dermal disorder.

Alopecia-mental retardation syndrome (APMR) is a rare autosomal recessive neuro-dermal disorder. It is characterized by heterogeneous phenotypic features, that is, absence of hair on the scalp, eyelashes, and eyebrows and mild to severe intellectual disability. So far, approximately 14 families (i.e., Iranian, Pakistani, and Swiss) with APMR have been reported in the scientific literature. Its precise prevalence is still unknown, but according to a predictive estimate, it prevails with the ratio of 1 in 1,000,000 persons worldwide. Until now, only four loci (two characterized and two uncharacterized) have been reported to be involved in APMR. The pathogenic variants in alpha-2-HS-glycoprotein [AHSG; APMR1 (MIM#203650)] and lanosterol synthase [LSS; APMR4 (MIM#618840)] are the characterized genetic factors associated with APMR. Among them, AHSG was reported in a consanguineous Iranian family and LSS gene in a Swiss origin family, while the remaining two uncharacterized loci, that is, APMR2 and APMR3, are reported in the Pakistani population. The current mini-report discusses the molecular genetics and mutational spectrum of APMR syndrome, its differential diagnosis from related disorders, and prediction of plausible candidate genes in two uncharacterized loci.

The molecular genetics of UV-Sensitive syndrome: A rare dermal anomaly.

Ultraviolet-sensitive syndrome is a rare skin disorder characterised by heterogeneous phenotypic spectrum of skin freckling, telangiectasia and acute sunburn. It usually has an autosomal recessive pattern. So far, only 18 patients from nine different families (Japanese, French, Israeli, Iranian and Pakistani) have been reported in scientific literature. Its precise prevalence is still unknown, but, according to an estimate, its prevalence ratio is 1:100,000 worldwide. Until now, only three genes have been reported to be involved in the syndrome; the Excision Repair Cross-Complementing, Group 6, the Excision Repair Cross-Complementing, Group 8 and the UV-Stimulated Scaffold Protein A (UVSSA). Among these genes, the last one is reported to be more prevalent among different ethnicities, including Pakistani. Physiologically, most of the syndrome genes are involved in the transcription-coupled nucleotide excision pathway. In order to reduce the disease severity, the patients are advised to use medicated skin moisturisers or sun-blocks, sunglasses and gloves, while going out in the sun to avoid sun exposure. The current narrative review was planned to discuss the molecular genetics and the mutational spectrum of the syndrome, and to describe the differential diagnosis of various related disorders in order to facilitate clinical researchers.

A flavonoid driven phyto-pharmacological effects of Capparis decidua Edgew. in rodents.

This study elicits the underlying mechanism(s) of Capparis decidua when used for different gut disorders. HPLC chromatogram of C. decidua extract (CD.Cr) and its respective fractions showed a variety of phytochemicals of which, kaempferol being in a high proportion. In mice, CD.Cr at doses of 70 and 150 mg/kg enhanced the wet feces output to 33 and 44% respectively as compared to carbachol (47.6%), while doses of 500 and 700 mg/kg, presented 41 and 70% safety against castor oil-driven diarrhea, respectively. Its flavonoid constituent, kaempferol at doses of (50 and 100 mg/kg) produced 51.7 and 82% safety when compared to nifedipine which provided 95% safety at dose of 40 mg/kg against castor oil-driven diarrhea like loperamide. In isolated jejunum preparations, C. decidua extract and its respective fractions (except pet-ether) produced atropine-sensitive inhibitory effects, whereas kaempferol and nifedipine showed atropine insensitive effects. Against high K+-induced contractions, C. decidua's fractions and kaempferol both exhibited a concentration-related non-specific inhibition while displacing the Ca++ -CRCs to right-ward with suppression in maximal response like nifedipine. In isolated rat ileal preparations, CD.Cr and respective fractions elicited atropine-sensitive gut excitatory responses. In summary, this article reports C. decidua's laxative effect through cholinergic receptor activation as well as its antidiarrheal effects, where its flavonoid constituent kaempferol produces Ca++ antagonist like activity, thus justifying C. decidua folk use in constipation and diarrhea.

Genetic studies of multiple consanguineous Pakistani families segregating oculocutaneous albinism identified novel and reported mutations.

Oculocutaneous albinism (OCA) is an autosomal-recessive disorder of a defective melanin pathway. The condition is characterized by hypopigmentation of hair, dermis, and ocular tissue. Genetic studies have reported seven nonsyndromic OCA genes, among which Pakistani OCA families mostly segregate TYR and OCA2 gene mutations. Here in the present study, we investigate the genetic factors of eight consanguineous OCA families from Pakistan. Genetic analysis was performed through single-nucleotide polymorphism (SNP) genotyping (for homozygosity mapping), whole exome sequencing (for mutation identification), Sanger sequencing (for validation and segregation analysis), and quantitative PCR (qPCR) (for copy number variant [CNV] validation). Genetic mapping in one family identified a novel homozygous deletion mutation of the entire TYRP1 gene, and a novel deletion of exon 19 in the OCA2 gene in two apparently unrelated families. In three further families, we identified homozygous mutations in TYR (NM_000372.4:c.1424G > A; p.Trp475*), NM_000372.4:c.895C > T; p.Arg299Cys), and SLC45A2 (NM_016180:c.1532C > T; p.Ala511Val). For the remaining two families, G and H, compound heterozygous TYR variants NM_000372.4:c.1037-7T > A, NM_000372.4:c.1255G > A (p.Gly419Arg), and NM_000372.4:c.1255G > A (p.Gly419Arg) and novel variant NM_000372.4:c.248T > G; (p.Val83Gly), respectively, were found. Our study further extends the evidence of TYR and OCA2 as genetic mutation hot spots in Pakistani families. Genetic screening of additional OCA cases may also contribute toward the development of Pakistani specific molecular diagnostic tests, genetic counseling, and personalized healthcare.

Ophthalmo-genetic analysis of Pakistani patients with nonsyndromic oculocutaneous albinism through whole exome sequencing.

Oculocutaneous albinism (OCA) is a disorder of defective melanin biosynthesis that is characterized by hypo-pigmentation of skin, hair and retinal pigment epithelium. Phenotypically, OCA patients exhibit white milky skin, whitish to golden hair and deterioration of retinal cells. Until recently, genetic studies have reported seven causative genes (TYR, TYRP1, OCA2, SLC45A2, SLC24A2, C10ORF11 and MCIR) and an uncharacterized OCA5 locus. Herein we present the medico-genetic study of three Pakistani patients inheriting autosomal recessive OCA. Whole exome sequencing, followed by Sanger DNA sequencing for segregation analysis, revealed recurrent mutations c.346C>T (p.Arg116*) and c.1255G>A (p.Gly419Arg) (family A and B respectively) in TYR gene, while the patient from family C did not reveal any known gene mutation, which suggests the involvement of some novel genetic factor. It is the first report of mapping c.346C>T mutation in a Pakistani patient. Our study further extends the evidence of genetic hotspots regions in TYR gene causing OCA in Pakistani population.

Exome sequence analysis identifies a homozygous, pathogenic, frameshift variant in the MAN2B1 gene underlying clinical variant of α-mannosidosis.

Background: α-mannosidosis (MAN) is a rare genetic condition that segregates in an autosomal recessive manner. Lack of lysosomal alpha-mannosidase is the underlying cause of the disease. Symptoms of the disease gradually worsen with the age. Newborns are usually asymptomatic, however, some cases are reported with either congenital ankle equinus or hydrocephalus during the first year. Primary symptoms are characterized by immune deficiency, hearing loss, skeletal abnormalities, progressive mental, motor and speech functions' impairment followed by facial asymmetry. Methods: We studied two Saudi families (A and B) with bilateral moderate hearing loss (family A) and clubfoot with glaucoma (family B). Clinical diagnosis was not reached based on phenotype of patients. Therefore, hypothesis-free whole exome sequencing (WES) was performed on DNA samples from affected individuals of both the families, followed by Sanger sequencing and segregation analysis to validate the segregation of the identified variant. Furthermore, 3D protein modelling was performed to determine the in silico effects of the identified variant on the protein structure and function. Results: Re-examination of clinical features revealed that the patients in family A have speech delay and hearing impairment along with craniostenosis, whereas the patients from family B have only clubfoot and glaucoma. WES identified a well known pathogenic homozygous frameshift variant (NM_000528.4: c.2402dupG; p.S802fs*129) in MAN2B1 in both the families. Sanger sequencing confirmed the segregation of the variant with the disease phenotype in both the families. 3D structural modeling of the MAN2B1 protein revealed significant changes in the tertiary structure of the mutant protein, which would affect enzyme function. This report presents a new case where partial and novel α-mannosidosis phenotypes are associated with a MAN2B1 gene pathogenic variant. Conclusion: Patients in both the families have manifested peculiar set of clinical symptoms associated with α-mannosidosis. Family A manifested partial clinical symptoms missing several characteristic features like intellectual disability, dysmorphic features, neurological and abdominal manifestations, whereas family B has no reported clinical symptoms related to α-mannosidosis except the novel symptoms including club foot and glaucoma which has never been reported earlier The current findings support the evidence that biallelic variants of MAN2B1 are associated with new clinical variants of α-mannosidosis.

Identification of GLI1 and KIAA0825 Variants in Two Families with Postaxial Polydactyly.

Polydactyly is a rare autosomal dominant or recessive appendicular patterning defect of the hands and feet, phenotypically characterized by the duplication of digits. Postaxial polydactyly (PAP) is the most common form and includes two main types: PAP type A (PAPA) and PAP type B (PAPB). Type A involves a well-established extra digit articulated with the fifth or sixth metacarpal, while type B presents a rudimentary or poorly developed superfluous digit. Pathogenic variants in several genes have been identified in isolated and syndromic forms of polydactyly. The current study presents two Pakistani families with autosomal recessive PAPA with intra- and inter-familial phenotype variability. Whole-exome sequencing and Sanger analysis revealed a novel missense variant in KIAA0825 (c.3572C>T: p.Pro1191Leu) in family A and a known nonsense variant in GLI1 (c.337C>T: p.Arg113*) in family B. In silico studies of mutant KIAA0825 and GLI1 proteins revealed considerable structural and interactional modifications that suggest an abnormal function of the proteins leading to the disease phenotype. The present study broadens the mutational spectrum of KIAA0825 and demonstrates the second case of a previously identified GLI1 variant with variable phenotypes. These findings facilitate genetic counseling in Pakistani families with a polydactyly-related phenotype.

Surface-enhanced Raman spectral characterization of antifungal activity of selenium and zinc based organometallic compounds.

Surface-enhanced Raman spectroscopy (SERS) is used to identify the biochemical changes associated with the antifungal activities of selenium and zinc organometallic complexes against Aspergillus niger fungus. These biochemical changes identified in the form of SERS peaks can help to understand the mechanism of action of these antifungal agents which is important for development of new antifungal drugs. The SERS spectral changes indicate the denaturation and conformational changes of proteins and fungal cell wall decomposition in complex exposed fungal samples. The SERS spectra of these organometallic complexes exposed fungi are analyzed by using statistical tools like principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA). PCA is employed to differentiate the SERS spectra of fungal samples exposed to ligands and complexes. The PLS-DA discriminated different groups of spectra with 99.8% sensitivity, 100% specificity, 98% accuracy and 86 % area under receiver operating characteristic (AUROC) curve.

Comparison of surface-enhanced Raman spectral data sets of filtrate portions of serum samples of hepatitis B and Hepatitis C infected patients obtained by centrifugal filtration.

BACKGROUND: Surface-enhanced Raman spectroscopy (SERS) is an efficient technique which has been used for the analysis of filtrate portions of serum samples of Hepatitis B (HBV) and Hepatitis C (HCV) virus. OBJECTIVES: The main reason for this study is to differentiate and compare HBV and HCV serum samples for disease diagnosis through SERS. Hepatitis B and hepatitis C disease biomarkers are more predictable in their centrifuged form as compared in their uncentrifuged form. For differentiation of SERS spectral data sets of hepatitis B, hepatitis C and healthy person principal component analysis (PCA) proved to be a helpful. Centrifugally filtered serum samples of hepatitis B and hepatitis C are clearly differentiated from centrifugally filtered serum samples of healthy individuals by using partial least square discriminant analysis (PLS-DA). METHODOLOGY: Serum sample of HBV, HCV and healthy patients were centrifugally filtered to separate filtrate portion for studying biochemical changes in serum sample. The SERS of these samples is performed using silver nanoparticles as substrates to identify specific spectral features of both viral diseases which can be used for the diagnosis and differentiation of these diseases. The purpose of centrifugal filtration of the serum samples of HBV and HCV positive and control samples by using filter membranes of 50 KDa size is to eliminate the proteins bigger than 50 KDa so that their contribution in the SERS spectrum is removed and disease related smaller proteins may be observed. Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) are statistical tools which were used for the further validation of SERS. RESULTS: HBV and HCV centrifugally filtered serum sample were compared and biomarkers including (uracil, phenylalanine, methionine, adenine, phosphodiester, proline, tyrosine, tryptophan, amino acid, thymine, fatty acid, nucleic acid, triglyceride, guanine and hydroxyproline) were identified through PCA and PLS-DA. Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) were used as a multivariate data analysis tool for the diagnosis of the characteristic SERS spectral features associated with both types of viral diseases. For the classification and differentiation of centrifugally filtered HBV, HCV, and control serum samples, Principal component analysis is found helpful. Moreover, PLS-DA can classify these two distinct sets of SERS spectral data with 0.90 percent specificity, 0.85 percent precision, and 0.83 percent accuracy. CONCLUSIONS: Surface enhanced Raman spectroscopy along with chemometric analysis like PCA and PLS-DA have been successfully differentiated HBV and HCV and healthy individuals' serum samples.

A GHRHR founder mutation causes isolated growth hormone deficiency type IV in a consanguineous Pakistani family.

Background: Isolated growth hormone deficiency (IGHD) is caused by a severe shortage or absence of growth hormone (GH), which results in aberrant growth and development. Patients with IGHD type IV (IGHD4) have a short stature, reduced serum GH levels, and delayed bone age. Objectives: To identify the causative mutation of IGHD in a consanguineous family comprising four affected patients with IGHD4 (MIM#618157) and explore its functional impact in silico. Methods: Clinical and radiological studies were performed to determine the phenotypic spectrum and hormonal profile of the disease, while whole-exome sequencing (WES) and Sanger sequencing were performed to identify the disease-causing mutation. In-silico studies involved protein structural modeling and docking, and molecular dynamic simulation analyses using computational tools. Finally, data from the Qatar Genome Program (QGP) were screened for the presence of the founder variant in the Qatari population. Results: All affected individuals presented with a short stature without gross skeletal anomalies and significantly reduced serum GH levels. Genetic mapping revealed a homozygous nonsense mutation [NM_000823:c.G214T:p.(Glu72*)] in the third exon of the growth-hormone-releasing hormone receptor gene GHRHR (MIM#139191) that was segregated in all patients. The substituted amber codon (UAG) seems to truncate the protein by deleting the C-terminus GPCR domain, thus markedly disturbing the GHRHR receptor and its interaction with the growth hormone-releasing hormone. Conclusion: These data support that a p.Glu72* founder mutation in GHRHR perturbs growth hormone signaling and causes IGHD type IV. In-silico and biochemical analyses support the pathogenic effect of this nonsense mutation, while our comprehensive phenotype and hormonal profiling has established the genotype-phenotype correlation. Based on the current study, early detection of GHRHR may help in better therapeutic intervention.

Surface-enhanced Raman spectroscopy for characterization of filtrate portions of blood serum samples of typhoid patients.

BACKGROUND: Surface-enhanced Raman spectroscopy (SERS) is explored to design a rapid screening method for the characterization and diagnosis of typhoid fever by employing filtrate fractions of blood serum samples obtained by centrifugal filtration with 50 KDa filters. OBJECTIVES: The purpose of this study, to separate the filtrate portions of blood serum samples in this way contain proteins smaller than 50 kDa and removal of bigger size protein which allows to acquire the SERS spectral features of smaller proteins more effectively which are probably associated with typhoid disease. Disease caused by Salmonella typhi diagnose more effectively by using surface-enhanced Raman spectroscopy (SERS) and multivariate data analysis tools. METHODS: SERS was used as a diagnostic tool for typhoid fever by comparison between healthy and diseased samples. For this purpose, all the samples were analyzed by comparing their SERS spectral features. Over the spectral range of 400-1800cm-1, multivariate data analysis techniques such as Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA) are applied to diagnose and differentiate different filtrate fractions of blood serum samples of patients of typhoid fever and healthy ones. RESULTS: By comparing SERS spectra of healthy filtrate with that of filtrate of typhoid sample, the SERS spectral features associated with disease development are identified including PCA is found to be efficient for the qualitative differentiation of all of the samples analyzed. Moreover, PLS-DA successfully identified and classified healthy and typhoid positive blood serum samples with 97 % accuracy, 99 % specificity, 91 % sensitivity and 0.78 area under the receiver operating characteristic (AUROC) curve. CONCLUSIONS: Surface enhanced Raman spectroscopy using silver nanoparticles SERS substrate, is found to be useful technique for the quick identification and evaluation of filtrate fractions of the blood serum samples of healthy and typhoid samples for disease diagnosis.

In Silico Analysis Identified Putative Pathogenic Missense nsSNPs in Human SLITRK1 Gene.

Human DNA contains several variations, which can affect the structure and normal functioning of a protein. These variations could be single nucleotide polymorphisms (SNPs) or insertion-deletions (InDels). SNPs, as opposed to InDels, are more commonly present in DNA and may cause genetic disorders. In the current study, several bioinformatic tools were used to prioritize the pathogenic variants in the SLITRK1 gene. Out of all of the variants, 16 were commonly predicted to be pathogenic by these tools. All the variants had very low frequency, i.e., <0.0001 in the global population. The secondary structure of all filtered variants was predicted, but no structural change was observed at the site of variation in any variant. Protein stability analysis of these variants was then performed, which determined a decrease in protein stability of 10 of the variants. Amino acid conservation analysis revealed that all the amino acids were highly conserved, indicating their structural and functional importance. Protein 3D structure of wildtype SLITRK1 and all of its variants was predicted using I-TASSER, and the effect of variation on 3D structure of the protein was observed using the Missense3D tool, which presented the probable structural loss in three variants, i.e., Asn529Lys, Leu496Pro and Leu94Phe. The wildtype SLITRK1 protein and these three variants were independently docked with their close interactor protein PTPRD, and remarkable differences were observed in the docking sites of normal and variants, which will ultimately affect the functional activity of the SLITRK1 protein. Previous studies have shown that mutations in SLITRK1 are involved in Tourette syndrome. The present study may assist a molecular geneticist in interpreting the variant pathogenicity in research as well as diagnostic setup.

Surface-enhanced Raman spectroscopy of polymerase chain reaction (PCR) products of Rifampin resistant and susceptible tuberculosis patients.

BACKGROUND: Raman spectroscopy is an effective tool for detecting and discriminating microorganisms that is robust, reliable, and rapid. OBJECTIVES: To develop a polymerase chain reaction technique (PCR) based on Surface Enhanced Raman Spectroscopy (SERS) technique with principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to assess diagnostic capability of SERS for distinguishing between tuberculosis (TB) positive rifampin resistant and tuberculosis (TB) positive rifampin susceptible samples. METHODS: Silver nanoparticles (Ag NPs) were used as SERS substrates and technique was used to distinguish TB positive rifampin (RIF) resistant and TB positive rifampin (RIF) susceptible patients on the basis of characteristic SERS spectral features of their respective PCR products. SERS spectra were acquired from 52 samples of PCR products including 22 samples of TB positive rifampin susceptible, 30 samples of TB positive rifampin resistant and negative control samples. All these samples were collected from individuals of same age. Furthermore, multivariate data analyses techniques such as PCA and PLS-DA were used to assess diagnostic capability of SERS for distinguishing between TB positive rifampin resistant and TB positive rifampin susceptible samples. RESULTS: PCA is found helpful for successful differentiation among these two groups of spectral data sets. Moreover, PLS-DA provides this classification quantitatively by predicting the class of SERS spectral data set with 73% area under curve, 96% sensitivity, 95.6% specificity and 95% accuracy. CONCLUSION: SERS can be employed for the rapid distinguishing between TB positive rifampin resistant and TB positive rifampin susceptible samples.

Pharmacological evaluation of Euphorbia hirta, Fagonia indica and Capparis decidua in hypertension through in-vivo and in vitro-assays.

OBJECTIVE: This study determines the efficacy and probable underlying mode of action to the folk usage of Euphorbia hirta, Fagonia indica and Capparis decidua in hypertension. METHODS: The aqueous-methanol extracts of E. hirta (EH.Cr), F. indica (FI.Cr) and C. decidua (CD.Cr) were tested for antihypertensive effects in rats using non-invasive and in-vasive blood pressure measuring apparatus. In-vitro assays were carried out using isolated rat aortae using PowerLab station. RESULTS: EH.Cr, FI.Cr and CD.Cr at 500 mg/kg (orally) caused a fall in the mean systolic blood pressure in arsenic-induced hypertensive and normotensive rats, similar to nifedipine. In rat aortae, EH.Cr, CD.Cr and FI.Cr reversed low (20 mM), high (80 mM) K+ and phenylephrine (P.E)-driven contractions, while F. indica partially inhibited high K+ contractions. In the presence of TEA, F. indica remained unable to relax low K+ contractions. EH.Cr and CD.Cr moved Ca++ concentrations response curves to the right, like nifedipine. All fractions of EH.Cr and CD.Cr except aqueous, pet-ether and chloroform fractions of FI.Cr displayed Ca++ antagonistic activity. FI.Cr, its ethyl acetate and aqueous fraction exhibited TEA-sensitive potassium channel activation. On baseline tension, test materials also produced phentolamine-sensitive vasospasm. CONCLUSION: E. hirta, F. indica and C. decidua possess antihypertensive activity in arsenic-induced hypertensive rats possibly mediated via endothelium-dependent vasorelaxation. In normotensive rats, E. hirta and C. decidua showed antihypertensive activities through endothelium-dependent and Ca++ antagonistic pathways, while F. indica exhibited potassium channel activation and Ca++ antagonistic like effects in its vasorelaxation. Additional weaker vasospastic effects were derived through α-adrenergic like pathways.

Establishment of Regional Concentration-Duration-Frequency Relationships of Air Pollution: A Case Study for PM2.5.

Poor air quality usually leads to PM2.5 warnings and affects human health. The impact of frequency and duration of extreme air quality has received considerable attention. The extreme concentration of air pollution is related to its duration and annual frequency of occurrence known as concentration-duration-frequency (CDF) relationships. However, the CDF formulas are empirical equations representing the relationship between the maximum concentration as a dependent variable and other parameters of interest, i.e., duration and annual frequency of occurrence. As a basis for deducing the extreme CDF relationship of PM2.5, the function assumes that the extreme concentration is related to the duration and frequency. In addition, the spatial pattern estimation of extreme PM2.5 is identified. The regional CDF identifies the regional extreme concentration with a specified duration and return period. The spatial pattern of extreme air pollution over 8 h duration shows the hotspots of air quality in the central and southwestern areas. Central and southwestern Taiwan is at high risk of exposure to air pollution. Use of the regional CDF analysis is highly recommended for efficient design of air quality management and control.

Spatial calibration and PM2.5 mapping of low-cost air quality sensors.

The data quality of low-cost sensors has received considerable attention and has also led to PM2.5 warnings. However, the calibration of low-cost sensor measurements in an environment with high relative humidity is critical. This study proposes an efficient calibration and mapping approach based on real-time spatial model. The study carried out spatial calibration, which automatically collected measurements of low-cost sensors and the regulatory stations, and investigated the spatial varying pattern of the calibrated low-cost sensor data. The low-cost PM2.5 sensors are spatially calibrated based on reference-grade measurements at regulatory stations. Results showed that the proposed spatial regression approach can explain the variability of the biases from the low-cost sensors with an R-square value of 0.94. The spatial calibration and mapping algorithm can improve the bias and decrease to 39% of the RMSE when compared to the nonspatial calibration model. This spatial calibration and real-time mapping approach provide a useful way for local communities and governmental agencies to adjust the consistency of the sensor network for improved air quality monitoring and assessment.

Spatiotemporal Analysis of Extracted Groundwater Volumes Estimated from Electricity Consumption.

Land subsidence caused by groundwater overexploitation is a serious global problem. The acquisition of spatiotemporal pumping rates and volumes is a first step for water managers to develop a strategic plan for mitigating land subsidence. This study investigates an empirical formulation to estimate the monthly maximum pumped volume over a 10-year period based on electric power consumption data. A spatiotemporal variability analysis of monthly pumped volume is developed to provide an improved understanding of seasonal pumping patterns and the role of irrigation type. The analysis of regional pumped volume provides an approximation of the spatiotemporal patterns of the variations in pumped volume. Results show the effects of climate, seasonal changes in pumping from irrigation, and the local differences in pumping caused to crop types. A seasonal pumped volume peak occurs annually, with the highest and least pumped volumes occurring in March (highest peak) and September (lowest peak), respectively. However, the majority of the historical maximum pumped volumes have occurred during the last few years. Extracted volumes continue to increase in some locations. The analysis reveals increasing trends in pumping, thereby possibly providing the locations where increased effective stresses may lead to land subsidence.