Neural Functions Enabled by a Polarity-Switchable Nanofluidic Memristor.

Reproducing neural functions with artificial nanofluidic systems has long been an aspirational goal for neuromorphic computing. In this study, neural functions, such as neural activation and synaptic plasticity, are successfully accomplished with a polarity-switchable nanofluidic memristor (PSNM), which is based on the anodized aluminum oxide (AAO) nanochannel array. The PSNM has unipolar memristive behavior at high electrolyte concentrations and bipolar memristive behavior at low electrolyte concentrations, which can emulate neural activation and synaptic plasticity, respectively. The mechanisms for the unipolar and bipolar memristive behaviors are related to the polyelectrolytic Wien (PEW) effect and ion accumulation/depletion effect, respectively. These findings are beneficial to the advancement of neuromorphic computing on nanofluidic platforms.

Bio-monitoring of Tissue Accumulation and Genotoxic Effect of Heavy Metals in Cyprinus carpio from River Kabul Khyber Pakhtunkhwa Pakistan.

The study explored (I) the concentration of heavy metals in water samples (II) their bioaccumulation in common carp Cyprinus carpio (III) and the subsequent genotoxicity in the selected organs of carp; from river Kabul, Khyber Pakhtunkhwa Pakistan. Except for Mercury (Hg) the water samples had all the heavy metals within permissible limits of recommended dietary allowance (RDA). Nonetheless a number of heavy metals (Zn, Ni, Cr, Cd, Pb and Hg) showed bioaccumulation at levels higher than permissible. Zinc (Zn) was the most while Cadmium (Cd) was the least accumulated metal in all tissue samples analyzed. The metal burden in different organs of C. carpio was in sequence of intestine > skin > liver > gills > muscle. The Comet assay established DNA damage in selected organs to be in accordance with metal burden; the most to least damage being in sequence of blood > intestine > skin > liver > gills > muscle. In conclusion assessment of DNA damage in the organs of C. carpio appears to be a useful bio-marker to evaluate genotoxic effects of heavy metal pollution.

Outcome of ilizarov fixator in complex non-union of long bones.

OBJECTIVE: To evaluate the efficacy of Ilizarov fixator in the management of complex non-union of long bones. METHODS: The retrospective study was conducted at Ayub Teaching Hospital, Abbottabad, and Khyber Teaching Hospital, Peshawar, Pakistan, and comprised data of patients aged 14- 60 years of either gender with complex non-union of long bones between January 2006 and December 2013. Data, including age, gender, mechanism of injury, type of long bone involved, complications of surgery and final outcome, was documented on a pre-designed proforma. Outcome was graded using Association for the Study and Application of Methods of Ilizarov scoring system. SPSS 20 was used for analysis. RESULTS: There were 45 patients of whom 30(66.7%) were males and 15(33.4%) were females. The overall mean age was 32.20±12.48 years (range: 14-60 years).Of the 45 non-unions, 39(86%) healed successfully, and the mean time to union was 30.69±8.6 weeks (range: 16-52weeks).In terms of outcome, 29(64.44%) patients had excellent bone results, 9(20%) had good results, 2(4.44%) had fair results and 5(11.1%) had poor bone results. There were 32(71.11%) patients with excellent functional result, 8(17.77%) good, 2(4.44%) fair and 3(6.66%) patients had poor results. CONCLUSIONS: Ilizarov fixator gave good and excellent results in complex non-union of long bones by eradicating the infection, filling the defect with bone transport, and correcting the deformity and limb length discrepancy.

Follicle-stimulating hormone receptor expression in soft tissue sarcomas.

AIMS: In adult humans, the follicle-stimulating hormone receptor (FSHR) is expressed only in the granulosa cells of the ovary and the Sertoli cells of the testis. Recently, it has been shown that FSHR is expressed selectively on the surface of blood vessels in a wide range of tumours. So far, the expression of FSHR in mesenchymal tumours has not been studied. METHODS AND RESULTS: We performed a semiquantitative evaluation of FSHR protein expression in a large cohort of soft tissue sarcomas (STS; n = 335), including 11 subtypes. FSHR-positive vessels were detected in all sarcoma subtypes analysed. Among liposarcomas, significantly more cases of dedifferentiated liposarcomas (28 of 44) showed FSHR expression compared to well-differentiated liposarcomas (WDLS; four of 21; P < 0.001). Vessels in lipomas (n = 9) and non-neoplastic fat were FSHR-negative. FSHR expression was also detected in tumour cells of all sarcoma subtypes examined, with the lowest incidence in WDLS (three of 21; 14.3%) and the highest frequency in undifferentiated high-grade pleomorphic sarcomas (41 of 60; 68.3%). CONCLUSIONS: These data supplement the previously reported results of FSHR expression in endothelial cells of various cancer types and form a solid basis for further studies of FSHR in mesenchymal neoplasms.

An updated review on cell signaling pathways regulated by candidate miRNAs in coronary artery disease.

MicroRNAs (miRNAs) are small endogenous non-coding RNA, size range from 17 to 25 nucleotides that regulate gene expression at the post-transcriptional level. More than 2000 different types of miRNAs have been identified in humans which regulate about 60% of gene expression, since the discovery of the first miRNA in 1993. MicroRNA performs many functions such as being involved in the regulation of various biological pathways for example cell migration, cell proliferation, cell differentiation, disease progression, and initiation. miRNAs also play an important role in the development of atherosclerosis lesions, cardiac fibroblast, cardiac hypertrophy, cancer, and neurological disorders. Abnormal activation of many cell signaling pathways has been observed in the development of coronary artery disease. Abnormal expression of these candidate miRNA genes leads to up or downregulation of specific genes, these specific genes play an important role in the regulation of cell signaling pathways involved in coronary artery disease. Many studies have found that miRNAs play a key role in the regulation of crucial signaling pathways that are involved in the pathophysiology of coronary artery disease. This review is designed to investigate the role of cell signaling pathways regulated by candidate miRNAs in Coronary artery disease.

Normal preoperative levels of gamma-glutamyltransferase predict the absence of common bile duct stones in patients scheduled for laparoscopic cholecystectomy: a retrospective cohort study.

Laparoscopic cholecystectomy, nowadays, is considered the gold standard option for management in patients diagnosed with symptomatic cholelithiasis. Nevertheless, some patients may have coexisting choledocholithiasis, which manifests later in life with grave complications such as cholangitis and pancreatitis. The objective of this study is to evaluate the role of preoperative gamma-glutamyltransferase (GGT) in predicting choledocholithiasis in patients undergoing laparoscopic cholecystectomy. Method: A total of 360 patients with symptomatic cholelithiasis based on diagnosis aided with abdominal ultrasound were included in the study. The study design was a retrospective cohort. Patients were evaluated based on a comparison between findings of per-operative cholangiogram and laboratory measure of GGT. Result: The mean age of study participants was 47.22 (±28.41) years. Mean GGT levels were 121.54 (±87.91) U/l. One hundred (27.7%) participants had raised GGT. But only 19.4% had been diagnosed with filling defect positive on cholangiogram. The predictability of GGT for positive cholangiogram is statistically significant at less than 0.001 with an area under the curve of 0.922 (0.887-0.957), sensitivity of 95.7%, specificity of 88.6%, and accuracy of 90%. The standard error reported (0.018) was found to be relatively low. Conclusion: Based on the provided information, it is concluded that GGT plays an important role in predicting the coexistence of choledocholithiasis in symptomatic cholelithiasis and can be used in the setting where the facility of per-operative cholangiogram is not available.

Endothelial follicle stimulating hormone receptor in primary kidney cancer correlates with subsequent response to sunitinib.

Sunitinib is an anti-angiogenic receptor tyrosine kinase inhibitor used to treat advanced metastatic renal cell carcinoma and other types of cancer. Sutent is effective in only approximately 70% of clear cell renal cell carcinoma (CCRCC) patients, has significant adverse side effects and no method is available to predict which patients will not respond. Our purpose was to explore the possibility of introducing an effective prediction method based on a marker of the tumour vasculature, the follicle stimulating hormone receptor (FSHR). Fifty patients diagnosed with advanced metastatic CCRCC have been subjected to surgery for removal of the primary tumour and were subsequently treated with sunitinib. After three months of therapy the patients were categorized as 'responsive', 'stable' or 'non-responsive' based on the RECIST guidelines. The blood vessel density and the percentage of FSHR-positive vessels were determined by immunofluorescence on sections from the primary tumours removed by surgery, prior to the sunitinib treatment. The percentage of FSHR-stained vessels was on average fivefold higher for the patients who responded to the treatment in comparison with the stable group and almost eightfold higher than in the non-responsive group. The percentage allowed the detection of responders with 87-100% sensitivity and specificity. No significant differences were detected in the total density of vessels among the three groups. The data suggest that FSHR expression levels in the blood vessels of CCRCC primary tumours can be used to predict, with high sensitivity and specificity, the patients who will respond to sunitinib therapy.

Genomic miscellany and allelic frequencies of Plasmodium falciparum msp-1, msp-2 and glurp in parasite isolates.

INTRODUCTION: The genomic miscellany of malaria parasites can help inform the intensity of malaria transmission and identify potential deficiencies in malaria control programs. This study was aimed at investigating the genomic miscellany, allele frequencies, and MOI of P. falciparum infection. METHODS: A total of 85 P. falciparum confirmed isolates out of 100 were included in this study that were collected from P. falciparum patients aged 4 months to 60 years in nine districts of Khyber Pakhtunkhwa Province. Parasite DNA was extracted from 200µL whole blood samples using the Qiagen DNA extraction kit following the manufacturer's instructions. The polymorphic regions of msp-1, msp-2 and glurp loci were genotyped using nested PCR followed by gel electrophoresis for amplified fragments identification and subsequent data analysis. RESULTS: Out of 85 P. falciparum infections detected, 30 were msp-1 and 32 were msp-2 alleles specific. Successful amplification occurred in 88.23% (75/85) isolates for msp-1, 78.9% (67/85) for msp-2 and 70% (60/85) for glurp gene. In msp-1, the K1 allelic family was predominantly prevalent as 66.66% (50/75), followed by RO33 and MAD20. The frequency of samples with single infection having only K1, MAD20 and RO33 were 21.34% (16/75), 8% (6/75), and 10.67% (8/75), respectively. In msp-2, both the FC27 and 3D7 allelic families revealed almost the same frequencies as 70.14% (47/67) and 67.16% (45/67), respectively. Nine glurp RII region alleles were identified in 60 isolates. The overall mean multiplicity of infection for msp genes was 1.6 with 1.8 for msp-1 and 1.4 for msp-2, while for glurp the MOI was 1.03. There was no significant association between multiplicity of infection and age groups (Spearman's rank coefficient = 0.050; P = 0.6) while MOI and parasite density correlated for only msp-2 allelic marker. CONCLUSIONS: The study showed high genetic diversity and allelic frequency with multiple clones of msp-1, msp-2 and glurp in P. falciparum isolates in Khyber Pakhtunkhwa, Pakistan. In the present study the genotype data may provide valuable information essential for monitoring the impact of malaria eradication efforts in this region.

Coronavirus Disease 2019 Pandemic Effects on Overseas Pakistanis Particularly Residing in China, Saudi Arabia and United Kingdom.

Aim: This study explored the Coronavirus Disease 2019 (COVID-19) pandemic effects on overseas Pakistani's residing in various parts of the world, particularly in China, Saudi Arabia (SA), and the United Kingdom (UK). Methods: This cross-sectional study was completed between November 2020 and April 2021. An online questionnaire was designed and circulated via various social media mediums to overseas Pakistani communities. The obtained data were statistically analyzed through SPSS version 19 for windows. P < 0.05 was considered statistically significant. Results: A total of 542 overseas Pakistani participated in the current study. In total, 157 (29%) were females and 385 (71%) males. There were 174 (32.1%), 142 (26.45%), 117 (21.6%), and 109 (19.85%) participants from the UK, SA, China, and other countries respectively. Some participants, or their family members, 93 (17.2%), got infected with the COVID-19. About one-third, 165 (30.4%), of the respondents were afraid that their company would violate their contracts or lose their jobs or be paid less. The majority, 469 (86.5%), believed that the lockdown is increasing their psychological stress. More than half of the participants, 314 (57.9%), stated that the Pakistani embassy did not facilitate them in their country of stay. About one-third, 194 (35.8%), of the respondents faced visa-related issues. More than one-third of respondents, 221 (40.8%), faced health issues due to lack of physical activities during the lockdown. Males were afraid that their company would violate their contract, lose jobs, or be paid less than females (p < 0.001). Both genders had psychological stress and health issues because of the pandemic. The participants from SA faced more visa-related issues, and they were less satisfied with the efforts of the Pakistani embassy to facilitate them compared to the UK and China participants (p = 0.013). Conclusion: Our data indicate that the COVID-19 pandemic impacted Pakistanis living in the UK, SA, China, and other parts of the world. They had health-related issues, visa problems and dissatisfaction with Pakistani embassy facilitations. Pakistanis living abroad require government assistance to resolve their issues.

A Plum On Thumb: A Rare Presentation Of Synovial Sarcoma.

Synovial sarcoma (SS) is a rare and aggressive mesenchymal tumour accounting for around 5-10% soft tissue neoplasms usually found in joints of upper and lower extremities. A 35years old healthy looking male patient from Afghanistan presented with swelling on palmar side of base of thumb from last one year. Seven months back excisional biopsy was taken report of which showed neurofibroma/dermatofibroma with. No evidence of malignancy seen. From last 5months mass reappeared and gradually increased in size with itching sensation and mild pain. On local examination there was 5×4×5 cm reddish mass on palmar surface of base of thumb with extension into mid thenar eminence with diffuse margins. X-ray showed soft tissue density mass with spikes of calcification. Ultrasound showed 4.2×4×4.5 cm heterogeneous solid lesion on anteromedial surface of root of right thumb without any remarkable intralesional calcification and remarkable intralesional vasculature. MRI reported lobulated well defined soft tissue mass eliciting low to intermediate signal on T1 and WIs and bright signal on T2and STIR Vividly enhancing mass. Case was operated mass was excised and biopsy sent. Post op status was unremarkable. Biopsy reported poorly differentiated biphasic synovial sarcoma. No recurrence seen till 3months.

Bioaccumulation of Heavy Metals in Water, Sediments, and Tissues and Their Histopathological Effects on Anodonta cygnea (Linea, 1876) in Kabul River, Khyber Pakhtunkhwa, Pakistan.

The present investigation aimed to assess the concentrations of selected heavy metals in water and sediments and their bioaccumulation in tissues of freshwater mussels and their histopathological effects on the digestive gland, gills, and gonads of Anodonta cygnea. Water, sediments, and freshwater mussel samples were collected at four sites, that is, reference and polluted sites, along the Kabul River, Khyber Pakhtunkhwa. The polluted sites were receiving effluents from the industrial, agricultural, municipal, and domestic sources. The order of metals in the water was Zn > Pb > Ni > Cu > Mn > Fe > Cr > Cd, in sediments the order was Fe > Zn > Cr > Ni > Mn > Pb > Cu > Cd, and in the soft tissues the order was Fe > Zn > Mn > Pb > Cu > Cr > Ni > Cd. Histopathological alterations observed in polluted sites of Kabul River were inflammation, hydropic vacuolation, and lipofuscin pigments (in digestive gland), gill lamellar fusion, dilated hemolymphatic sinus, clumping, and generation of cilia and hemocytic infiltration (in gills), and atresia, necrosis, granulocytoma, hemocytic infiltration, and lipofuscin pigments (in gonads). The histopathological alterations in the organs of Anodonta cygnea can be considered as reliable biomarkers in biomonitoring of heavy metal pollution in aquatic ecosystems.

Bioaccumulation of Heavy Metals in Different Organs of Wallago attu from River Kabul Khyber Pakhtunkhwa, Pakistan.

The aim of the study was to quantify the accumulation of heavy metals like Zn, Ni, Cr, Cu, Cd, Mn, Fe, and Hg in various organs of Wallago attu. Samples were collected from polluted parts of River Kabul and compared with control fish netted from Warsak Dam. The data indicated that the sequence of metal bioaccumulation in the skin, gills, and muscle was Zn > Cr > Pb > Cu > Ni > Fe > Mn > Hg > Cd, in the intestine was Zn > Pb > Cr > Cu > Ni > Fe > Mn > Hg > Cd, and in the liver was Zn > Pb > Cr > Cu > Ni > Fe > Mn > Hg > Cd. The overall metal burden in different tissues of W. attu was in the sequence of skin > gills > intestine > muscle > liver. The skin being the prime target organ showed that the route of metal uptake was the direct result of fish to metal exposure. The liver accumulated the least level of metals than other organs of the same fish.

Pollution Problem in River Kabul: Accumulation Estimates of Heavy Metals in Native Fish Species.

The contamination of aquatic systems with heavy metals is affecting the fish population and hence results in a decline of productivity rate. River Kabul is a transcountry river originating at Paghman province in Afghanistan and inters in Khyber Pakhtunkhwa province of Pakistan and it is the major source of irrigation and more than 54 fish species have been reported in the river. Present study aimed at the estimation of heavy metals load in the fish living in River Kabul. Heavy metals including chromium, nickel, copper, zinc, cadmium, and lead were determined through atomic absorption spectrophotometer after tissue digestion by adopting standard procedures. Concentrations of these metals were recorded in muscles and liver of five native fish species, namely, Wallago attu, Aorichthys seenghala, Cyprinus carpio, Labeo dyocheilus, and Ompok bimaculatus. The concentrations of chromium, nickel, copper, zinc, and lead were higher in both of the tissues, whereas the concentration of cadmium was comparatively low. However, the concentration of metals was exceeding the RDA (Recommended Dietary Allowance of USA) limits. Hence, continuous fish consumption may create health problems for the consumers. The results of the present study are alarming and suggest implementing environmental laws and initiation of a biomonitoring program of the river.