2-D Slicewise Waveform Inversion of Sound Speed and Acoustic Attenuation for Ring Array Ultrasound Tomography Based on a Block LU Solver.

Ultrasound tomography is an emerging imaging modality that uses the transmission of ultrasound through tissue to reconstruct images of its mechanical properties. Initially, ray-based methods were used to reconstruct these images, but their inability to account for diffraction often resulted in poor resolution. Waveform inversion overcame this limitation, providing high-resolution images of the tissue. Most clinical implementations, often directed at breast cancer imaging, currently rely on a frequency-domain waveform inversion to reduce computation time. For ring arrays, ray tomography was long considered a necessary step prior to waveform inversion in order to avoid cycle skipping. However, in this paper, we demonstrate that frequency-domain waveform inversion can reliably reconstruct high-resolution images of sound speed and attenuation without relying on ray tomography to provide an initial model. We provide a detailed description of our frequency-domain waveform inversion algorithm with open-source code and data that we make publicly available.

Novel mutations in CYBB Gene Cause X-linked chronic Granulomatous Disease in Pakistani patients.

BACKGROUND: Chronic Granulomatous Disease (CGD) is a primary immunodeficiency that causes susceptibility to recurrent fungal and bacterial infections. The CYBB gene encodes gp91phox component of the Phagocytic Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and specifically, X-linked CGD is caused by mutations in the CYBB gene, located on the X chromosome. The aim of the study was to characterize functional and genetic mutations in X-linked CGD. METHODS: Functional analysis was conducted on the whole blood of seventeen male individuals who were suspected to have X-linked chronic granulomatous disease (CGD). Flow cytometry was employed to assess the capacity of NADPH oxidase, measuring both H2O2 production and gp91phox protein expression in neutrophils. Additionally, DNA Sanger sequencing was performed for genetic analysis. The pathogenicity of novel mutations was assessed by pathogenicity prediction tools. RESULT: Among the seventeen patients evaluated, five patients (P1, P2, P3, P4, and P5) displayed impaired H2O2 production by their neutrophils upon stimulation with Phorbol myristate acetate (PMA), accompanied by abnormal gp91phox expression. DNA sequencing of the CYBB gene identified specific mutations in each patient. In P1 and P2 (previously reported cases), a hemizygous missense mutation, c.925G > A/p.E309K was identified. In P3 and P4 (novel cases), hemizygous nonsense mutations, c.216T > A/p.C72X were found. Lastly, in P5 (also a novel case), a hemizygous missense mutation, c.732T > G/p.C244W was detected. These mutations reside in exons 9,3 and 7 of the CYBB gene, respectively. CONCLUSIONS: The current study contributes to the understanding of the clinical and genetic spectrum associated with X-linked chronic granulomatous disease (CGD). It highlights the significance of early diagnosis in CGD and emphasizes the importance of lifelong prophylaxis to prevent severe infections.

Prevalence and Molecular Characterization of Cystic Echinococcosis in Livestock Population of the Malakand Division, Khyber Pakhtunkhwa, Pakistan.

Cystic echinococcosis (CE) is a neglected zoonotic disease prevalent in Pakistan, but the genetic diversity of the cestode is largely unexplored in the country. This study investigated the molecular epidemiology of CE infecting the livestock population of the Malakand division, Khyber Pakhtunkhwa, Pakistan. A total of 1,200 livestock, including buffaloes, cattle, goats, and sheep, were examined for echinococcosis from November 2017-2018 at different slaughterhouses in the Malakand division. Hydatid cysts were collected from different organs, and hydatid cyst fluid (HCF) was examined microscopically and used for DNA extraction. The LSU (rrnl) and NAD1 genes were amplified and sequenced. The overall prevalence of CE was 17% (204/1,200), including cows (21.7%), buffaloes (17.4%), goats (10%), and sheep (9.6%). The infection was relatively more prevalent among males (17%) than females (16.9%) and animals of older age (>5 years) (p = 0.710). Liver (63.2%) and lungs (25%) were more affected as compared to kidneys (6.8%) and heart (4.9%). HCF analysis indicated that 52.0% of the cysts were sterile and (48.0%) were fertile. Sequencing and phylogenetic analyses confirmed 80.0% of the isolates as Echinococcus granulosus sensu stricto (G1-G3) in all animal species, while Echinococcus equinus (G4) and Echinococcus ortleppi (G5) were present in buffaloes. The present study concluded that CE is prevalent in the livestock population of Malakand. Besides E. granulosus s. s. (G1-G3), E. ortleppi genotype (G5) and E. equinus (G4) in livestock were also reported.

Medicinal Animals and Plants as Alternative and Complementary Medicine in Southern Regions of Khyber Pakhtunkhwa, Pakistan.

Background: Local communities use animals and plants as common traditional therapies for various diseases. The study aimed to document animals and animal-plant mixture recipes that are used as alternative and complementary medicine in southern regions of Khyber Pakhtunkhwa, Pakistan. Methods: The data were collected (2017-2018) in three remote areas (Dera Ismail Khan, Bannu, and Lakki Marwat) through questionnaires and face-to-face interviews with local inhabitants. Data on ethnomedicinal uses and cultural values of animal products or parts and their mixture with plants were analyzed using various indices such as frequency of citation (FC), informant consensus (FIC), and fidelity level (FL) to find the highly preferred species in the area. Results: A total of 185 informants (117 females and 68 males) were interviewed. The study documented 32 animal species, vertebrates (n = 24) and invertebrates (n = 8), for curing 37 types of diseases. Mammals (n = 13) were among the most commonly utilized species followed by birds (n = 8), arthropods (n = 7), reptiles (n = 2), and fishes and annelids (n = 1 each). Among the reported animals, Herpestes edwardsi (mongoose), Macaca mulatta (monkey), Labeo rohita (rohu), Oryctolagus cuniculus (rabbit), and Streptopelia decaocto (dove) were the newly reported species used as alternative medicine. The meat of Capra hircus (goat), monkey, and rabbit was used to treat chronic diseases such as hepatitis C, cancer, epilepsy, and asthma. A total of 17 plants belonging to 15 botanical families were used in combination with animal parts/products. The commonly used families were Piperaceae (31%) followed by Apiaceae (27%). The notable plant species in combination with animal products were Curcuma longa, Piper nigrum, Coriandrum sativum, Brassica rapa, and Phoenix dactylifera. Seeds were the highest used part in animal-plant mixture recipes. Gallus gallus (chicken) and Columba livia (pigeon) secured the highest (FC = 28) and (FL = 80%), respectively. FIC results had shown the highest degree of consensus for general body weakness (FIC = 0.88) and pyrexia (FIC = 0.86). Conclusion: Our findings suggest that local communities in the southern regions of Khyber Pakhtunkhwa have substantial knowledge about the formulation of ethnomedicines from both flora and fauna that need urgent documentation to avoid eroding and for conservational purposes. The newly reported phytozootherapeutic recipes and animal species can potentially be a source of pharmacologically active constituents and should be checked experimentally for further confirmation.

Cystic echinococcosis: an emerging zoonosis in southern regions of Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Cystic echinococcosis (CE) is one of the principal causes of economic loss to the livestock industry because of its morbidity and mortality of food-producing animals and condemnation of important visceral organs. Pakistan being an agricultural country having an extensive livestock sector, is mostly practiced by poor people, which has a fundamental role in the economy. The present study was aimed to conduct a cross-sectional survey and PCR based confirmation of Echinococcus granulosus in sheep, goats, cows, and buffaloes from southern regions (three districts: Lakki Marwat, Bannu, and Karak) of Khyber Pakhtunkhwa, Pakistan. During the study, a total of 2833 animals were examined randomly including; sheep (n = 529), goats (n = 428), cows (n = 1693), and buffaloes (n = 183). Hydatid cysts were collected and examined for the presence of protoscoleces using microscopy. Detection of DNA was performed by using PCR and two mitochondrial genetic markers namely; NAD-1 and COX-1 were amplified. RESULTS: The overall prevalence of CE was found to be (9%) among the examined animals. The hydatid cyst infection was highly prevalent in buffaloes (12%), followed by sheep (10%), cows (9%), and goats (5.1%). Cystic echinococcosis was more prevalent (10%; 96/992) in district Lakki Marwat followed by district Bannu (9%; 112/1246) and Karak (7%; 39/595). Female animals were more likely to be infected with CE (11.6%) than male animals (5.3%) (p = 0.001). Similarly, the infection was higher in the older group of animals as compared to younger (p = 0.001). Mostly (52.2%; n = 129) of hydatid cysts were found in the liver, while (64.4%; n = 159) cysts of the infected animals were infertile. PCR based identification confirmed the presence of E. granulosus sensu stricto (s.s) in the study area. CONCLUSION: Cystic echinococcosis was found to be highly prevalent in southern regions of Khyber Pakhtunkhwa and could be a potential threat to human health. Moreover, molecular sequencing and phylogenetic analyses should be carried out in future to identify the prevailing genotype (s) of E. granulosus s.s.

A systematic review of medicinal plants used against Echinococcus granulosus.

Cystic echinococcosis (CE) is a zoonotic helminthiasis caused by different species of the genus Echinococcus, and is a major economic and public health concern worldwide. Synthetic anthelmintics are most commonly used to control CE, however, prolonged use of these drugs may result in many adverse effects. This study aims to discuss the in vitro/in vivo scolicidal efficacy of different medicinal plants and their components used against Echinococcus granulosus. Google Scholar, ScienceDirect, PubMed and Scopus were used to retrieve the published literature from 2000-2020. A total of 62 published articles met the eligibility criteria and were reviewed. A total of 52 plant species belonging to 22 families have been reported to be evaluated as scolicidal agents against E. granulosus worldwide. Most extensively used medicinal plants against E. granulosus belong to the family Lamiaceae (25.0%) followed by Apiaceae (11.3%). Among various plant parts, leaves (36.0%) were most commonly used. Essential oils of Zataria multiflora and Ferula asafetida at a concentration of 0.02, and 0.06 mg/ml showed 100% in vitro scolicidal activity after 10 min post application, respectively. Z. multiflora also depicted high in vivo efficacy by decreasing weight and size while also causing extensive damage to the germinal layer of the cysts. Plant-based compounds like berberine, thymol, and thymoquinone have shown high efficacy against E. granulosus. These plant species and compounds could be potentially used for the development of an effective drug against E. granulosus, if further investigated for in vivo efficacy, toxicity, and mechanism of drug action in future research.