Role of nanotechnology in animal production and veterinary medicine.

Nanotechnology is the discipline and technology of small and specific things that are < 100 nm in size. Because of their extremely miniscule size, any changes in their chemical and physical structure may show higher reactivity and solubility than larger particles. Nanotechnology plays a vital role in every field of life. It is considered one of the most bleeding edge field of scientific research. It has already several applications in a myriad of disciplines while its application in the field of animal production and veterinary medicine is still experimental in nature. But, in recent years, the role of nanotechnology in the aforementioned fields of scientific inquiry has shown great progress. These days, nanotechnology has been employed to revolutionize drug delivery systems and diagnose atypical diseases. Applications of nanoparticle technology in the field of animal reproduction and development of efficacious vaccines have been at the forefront of scientific endeavors. Additionally, their impacts on meat and milk quality are also being judiciously inquired in recent decades. Veterinary nanotechnology has great potential to improve diagnosis and treatment, and provide new tools to this field. This review focuses on some noteworthy applications of nanoparticles in the field of animal production and their future perspectives.

The first report on serotyping of bluetongue virus in small ruminants of Khyber Pakhtunkhwa province, Pakistan.

Bluetongue virus (BTV), a member of Orbivirus genus (family Reoviridae), is a non-contagious infection of domestic and wild ruminants. The current study was designed to detect various serotypes of BTV in small ruminants of Khyber Pakhtunkhwa (KPK) province of Pakistan, along with their effects on hemato-biochemical parameters. A total of 408 serum samples in four districts (Mansehra, Abbottabad, Swabi, and Kohat) of KPK from small ruminants were screened based on competitive ELISA (cELISA). A total of 204 (50%) samples were found positive for BTV group-specific antibodies. The seropositive samples were processed for the detection of BTV serotypes through real-time polymerase chain reaction (qPCR). Out of 204 cELISA-positive samples, 60 (29.41%) were found positive through qPCR. Three serotypes [6, 8, 9] were detected from Mansehra District and two from Kohat [2, 8] and Abbottabad [6, 8], while only one from Swabi [8]. The serotype "8" was found consistently in all the four study districts. A significant (p < 0.05) increase in the level of blood urea nitrogen (BUN) and alkaline phosphatase (ALP) was recorded in goats, whereas aspartate aminotransferase (AST) in sheep infected with BTV, compared to healthy animals. The hematological parameters showed significantly (p < 0.05) raised total leucocyte count (TLC) in both sheep and goats, whereas only hematocrit (HCT) value was increased significantly (p < 0.05) in infected sheep. This is the first report on serotyping of BTV among small ruminants in Pakistan.

Efficacy and safety of ertapenem dosing in patients with ESBL producing Enterobacterales infections utilizing renal replacement therapies.

PURPOSE: The clinical efficacy and safety of ertapenem use in patients undergoing renal replacement therapies (RRT) are not well-documented. Therefore, we aimed to investigate the safety and efficacy of ertapenem in patients with sepsis secondary to Enterobacterales who are undergoing RRT. METHODS: A retrospective cohort study was conducted on patients who met the inclusion criteria at our hospital between May 2015 and December 2021. The primary endpoint was 30-day mortality. Secondary endpoints included clinical cure, microbiologic cure, recurrence rate, and incidence of seizures. RESULTS: During the study period, 158 patients met the inclusion criteria. Of these, 86 were male (54.4%), the mean age was 66.4 ± 13.8 years, and the mean weight was 77 ± 22.4 kg. The most common diagnosis was bacteremia in 48 (30.4%) subjects, followed by urinary tract infection in 39 (24.7%) subjects, and pneumonia in 35 (22.2%) patients. The most isolated pathogens were Escherichia coli, followed by Klebsiella species. The median ertapenem dose was 0.5 g intravenously (IV) daily in those who received intermittent hemodialysis (IHD) and 1 g IV daily for those who received continuous veno-venous hemofiltration (CVVH). The 30-day mortality rate was 24%, the clinical cure rate was 89.2%, the microbiologic cure rate was 82%, the 30-day recurrence rate was 41.1%, and the incidence of seizures was 2.5%. Multivariate logistic regression analysis indicated that age (OR 1.04 [95% CI: 1.003-1.075]), being critically ill at therapy initiation (OR 2.9 [95% CI: 1.1-7.5]), and Enterobacterales other than Klebsiella species and Escherichia coli (OR 3.8 [95% CI: 1.1-12.5]) were significant independent risk factors associated with mortality in this population. Ertapenem dose was not associated with mortality. CONCLUSION: Our findings suggest that the commonly used doses of ertapenem in patients undergoing IHD and CVVH are clinically effective but may pose a higher risk of seizures. A comprehensive pharmacokinetic study is needed to determine the most effective and safe dose for this population.

Genetic diversity of cucumber green mottle mosaic virus (CGMMV) infecting cucurbits.

Cucumber green mottle mosaic virus (CGMMV), a well-known Tobamovirus, infects cucurbits across the globe. To determine its current status, molecular characterization, genetic recombination, gene flow and selection pressure, 10 districts from Punjab province of Pakistan were surveyed and a total of 2561 cucurbits samples were collected during 2019-2020. These samples were subjected to virus-specific double antibody sandwich-enzyme linked immunosorbent assay (DAS-ELISA) for the detection of CGMMV. The results revealed that viral disease was prevalent in all surveyed districts of Punjab with an overall 25.69% disease incidence. ELISA positive samples were further confirmed through RT-PCR and sequencing of coat protein (CP) cistron. Sequence analysis showed that the present studied CGMMV isolates have 96-99.5% nucleotide and 94.40-99.50% amino acid identities with those already available in GenBank. Phylogenetic analysis also revealed that understudied isolates were closely related with South Korean (AB369274) and Japanese (V01551) isolates and clustered in a separate clad. Sequence polymorphisms were observed in 663 bp of sequence within 31 CGMMV isolates covering complete CP gene. Total number of sites were 662, of which 610 and 52 sites were monomorphic and polymorphic (segregating), respectively. Of these polymorphic, 24 were singleton variable and 28 were parsimony informative. Overall nucleotide diversity (π) in all the understudied 31 isolates was 0.00010 while a total of 1 InDel event was observed and InDel Diversity (k) was 0.065. Haplotype diversity analysis revealed that there was a total 29 haplotypes with haplotype diversity (Hd) of 0.993458 in all the 31 isolates which provide evidence of less diversity among Pakistani isolates. The statistical analysis revealed the values 2.568, 5.31304 and 4.86698 of Tajima's D, Fu, & Li's F* and D*, respectively, which witnessed the population of CGMMV was under balanced selection pressure.

CCL18 in peritoneal dialysis patients and encapsulating peritoneal sclerosis.

BACKGROUND: Peritoneal fibrosis manifests clinically as membrane failure or encapsulating peritoneal sclerosis (EPS). There are no clinical or biochemical tests to determine the rate of progression of peritoneal fibrosis. CCL18/pulmonary and activation-regulated chemokine (PARC) is profibrotic and stimulates collagen production independent of the effect of transforming growth factor beta. This has not been studied in peritoneal dialysis (PD) patients. MATERIALS AND METHODS: We have prospectively studied 106 patients, free from infection/recent peritonitis. A high concentration of CCL18 was discovered by multiplex antibody arrays and quantified by ELISA. Serum and dialysate levels were examined for their prognostic values. RESULTS: By multiple regression analysis, dialysate CCL18 (6·76 ± 0·66 µg 4 h⁻¹) correlated with increasing membrane transport status (TS) (P < 0·0001) and total glucose exposure/24 h (P = 0·033). Serum CCL18 correlated with high TS (P = 0·0001) and duration of PD (P = 0·001). After 12 months of follow-up, 57 patients remained on PD while 12 patients were transferred to haemodialysis (HD) and seven developed EPS. Patients who subsequently developed EPS had higher baseline dialysate CCL18 (11·5 ± 3·6 µg 4 h⁻¹ vs. 5·6 ± 0·82 µg 4 h⁻¹, P = 0·03) and serum CCL18 (156·9 ± 12·8 ng mL⁻¹ vs. 124·8 ± 12·2 ng mL⁻¹, P = 0·02) compared with the stable PD group. CONCLUSION: This is the first report of high levels of CCL18 in the spent dialysate and serum from long-term PD patients. These levels correlated with dysfunction of peritoneal membrane transport status, therefore following CCL18 in a longitudinal study may be of interest.

Sero-epidemiology of bluetongue virus (BTV) infection in sheep and goats of Khyber Pakhtunkhwa province of Pakistan.

Bluetongue virus (BTV) infection is an emerging hazard in small ruminants having socio-economic impacts on animals and associated people. The current study was aimed to estimate the sero-prevalence and associated risk factors in sheep and goat from Khyber Pakhtunkhwa (KP) province of Pakistan. Three distinct zones (northern, central and southern) with four districts (Mansehra, Abbottabad, Swabi, and Kohat) with a higher population of small ruminants were selected. A total of n = 408 sera originating from sheep (n = 212) and goats (n = 196) were randomly collected for detection of BTV group specific antibodies through competitive ELISA (c-ELISA). Univariable and multiple logistic regressions were applied to assess the potential risk factors associated with the occurrence of this disease. Results showed an overall prevalence of 50.00% (CI = 44.17-54.83) of BTV in both sheep and goats with a significant difference (p < 0.05) among different districts. The prevalence of BTV in sheep was found higher (56.60%, CI = 49.6-63.4) than goats (42.86%, CI = 35.8-50.1). The risk factors identified based on chi-square test were; 1-2 year of animals, herd size and location in sheep while, milking status, ticks infestation, location and herd size for goats (p < 0.05). On the basis of univariable analysis, 1-2 year of animals, and location for sheep while, ticks infestation and location for goats (OR > 1). Multiple logistic regressions conferred only herd size and location as potential risk factors (OR > 1) for BTV in sheep and goats. The study concluded higher prevalence of BTV in sheep than the goats, the risk factors were significantly associated with the occurrence of disease, and together ascertaining the needs to design appropriate disease management and control strategies in sheep and goats.

Peritonitis, peritoneal inflammation and membrane permeability: a longitudinal study of dialysate and serum MCP-1 in stable patients on peritoneal dialysis.

BACKGROUND: Increase in peritoneal membrane permeability (D/P) correlates with systemic and peritoneal markers of inflammation and neoangiogenesis. Monocyte chemoattractant protein-1 (MCP-1, CCL2) is a potent chemoattractant and activator of monocytes/macrophages. We measured the serum (sMCP-1) and dialysate MCP-1 (dMCP-1) concentrations of stable peritoneal dialysis (PD) patients and studied various factors affecting MCP-1 production. We also looked at the correlation of dMCP-1 concentrations with change in D/P over 12 months. METHODS: Forty-five stable prevalent and 6 new PD patients (22 CAPD, 29 APD) were studied. Median PD duration was 21 months (range 1-114). D/P was measured by standardized peritoneal equilibration test (PET). Patients with recent peritonitis within 3 months of the start of study were excluded. MCP-1 concentrations were measured in serum, overnight dialysate and post-PET dialysate, both at baseline and at 12 months by ELISA. RESULTS: On univariate analysis, post-PET dMCP-1 concentrations positively correlated with sMCP-1 (p=0.0002), duration of PD (p=0.02), dialysate volume (p=0.001), peritoneal creatinine clearance (p=0.0002) and D/P (p=0.001). There was a negative correlation with residual renal function (p=0.001). dMCP-1 concentrations were higher in patients with past peritonitis (p=0.001). On multivariate analysis, factors independently associated with dMCP-1 were sMCP-1 (p=0.003) and past peritonitis (p=0.001). Thirty patients completed this study, and D/P rose by > 0.1 in 20% patients. dMCP-1 concentrations were higher in baseline and 12-month samples in patients with change in D/P >0.1. CONCLUSIONS: We conclude that dMCP-1 concentrations are related to past peritonitis and serum MCP-1. It is difficult to interpret the relationship of dMCP-1 with change in D/P over time due to the small number of patients.

Dynamics of land use and land cover change (LULCC) using geospatial techniques: a case study of Islamabad Pakistan.

One of the detailed and useful ways to develop land use classification maps is use of geospatial techniques such as remote sensing and Geographic Information System (GIS). It vastly improves the selection of areas designated as agricultural, industrial and/or urban sector of a region. In Islamabad city and its surroundings, change in land use has been observed and new developments (agriculture, commercial, industrial and urban) are emerging every day. Thus, the rationale of this study was to evaluate land use/cover changes in Islamabad from 1992 to 2012. Quantification of spatial and temporal dynamics of land use/cover changes was accomplished by using two satellite images, and classifying them via supervised classification algorithm and finally applying post-classification change detection technique in GIS. The increase was observed in agricultural area, built-up area and water body from 1992 to 2012. On the other hand forest and barren area followed a declining trend. The driving force behind this change was economic development, climate change and population growth. Rapid urbanization and deforestation resulted in a wide range of environmental impacts, including degraded habitat quality.

A System for True and False Memory Prediction Based on 2D and 3D Educational Contents and EEG Brain Signals.

We studied the impact of 2D and 3D educational contents on learning and memory recall using electroencephalography (EEG) brain signals. For this purpose, we adopted a classification approach that predicts true and false memories in case of both short term memory (STM) and long term memory (LTM) and helps to decide whether there is a difference between the impact of 2D and 3D educational contents. In this approach, EEG brain signals are converted into topomaps and then discriminative features are extracted from them and finally support vector machine (SVM) which is employed to predict brain states. For data collection, half of sixty-eight healthy individuals watched the learning material in 2D format whereas the rest watched the same material in 3D format. After learning task, memory recall tasks were performed after 30 minutes (STM) and two months (LTM), and EEG signals were recorded. In case of STM, 97.5% prediction accuracy was achieved for 3D and 96.6% for 2D and, in case of LTM, it was 100% for both 2D and 3D. The statistical analysis of the results suggested that for learning and memory recall both 2D and 3D materials do not have much difference in case of STM and LTM.

Autoimmune pancreatitis mimicking Klatskin tumour on radiology.

Autoimmune pancreatitis (AIP) is categorised into two distinct types, AIP type 1 and 2. Although there can be multisystem involvement, rarely, the cholangitis associated with AIP can present radiologically in a manner similar to that of Klatskin tumour. We present the case of a 65-year-old man who was almost misdiagnosed with a Klatskin tumour because of the similarity in radiological features of the two aforementioned clinical entities. The patient presented with a history of jaundice, pruritus and abdominal pain, and work up showed deranged liver function tests, elevated cancer antigen 19-9 levels and positive antinuclear antibodies. CT scan of the abdomen showed findings suggestive of Klatskin tumour but due to diffuse enlargement of the pancreas and surrounding low-attenuation halo found on a closer review, a diagnosis of AIP was performed. The patient was started on standard corticosteroid therapy and responded well, with complete resolution of the radiological findings.

Neurofibromatosis type 2 patient presenting with medulloblastoma.

BACKGROUND: Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome with a frequency of 1 in 25,000 live births and a penetrance of almost 100% by the sixth decade of life. The main tumors occurring in NF2 patients are bilateral vestibular schwannomas, other peripheral, cranial and spinal nerve schwannomas, intracranial and intraspinal meningiomas, ependymomas, and gliomas. CASE DESCRIPTION: We report the case of a 6-year-old boy who presented with a 1-month history of nausea and recurrent vomiting. Physical examination was positive for ataxic gait and left-sided facial nerve palsy. Family history was positive for NF2 in the patient's father and paternal uncle. Magnetic resonance imaging brain revealed a solid enhancing lesion arising from the right cerebellar cortex, which was effacing the fourth ventricles and causing hydrocephalus. Craniotomy and excision of the lesion were performed. Histopathology report confirmed the diagnosis to be desmoplastic medulloblastoma. Based on the patients' subsequent history and family history, he was diagnosed to be a case of NF2. CONCLUSION: This is the first case of medulloblastoma occurring in a patient with NF2 and raises the possibility of an association between medulloblastoma and NF2.

Bullous scabies: a case report and review of the literature.

BACKGROUND: Scabies is a common parasitic infection caused by the mite Sarcoptes Scabiei. About 300 million cases of scabies are reported annually. Scabies usually presents clinically with an erythematous excoriated papulovesicular rash, burrows, nodules and hyperkeratotic lesions in specific body areas. A rare presentation of scabies is the bullous pemphigoid-like bullous scabies. So far, to the best of our knowledge, only 32 cases of bullous scabies have been reported in medical literature, of which only 11 were under 60 years of age at the time of initial presentation. This is the first case of bullous scabies being reported from Pakistan. CASE PRESENTATION: Herein we discuss, with reference to the existing literature, the case of a 23-year-old Punjabi male who presented with a 3 day history of a tense, non-erythematous, non-tender bulla measuring approximately 0.5 cm x 0.8 cm on the right foot near the interdigital cleft. He was diagnosed to have bullous scabies. CONCLUSION: The diagnosis of scabies should be considered in all patients who present with tense bullous lesions accompanied by pruritus and a maculopapular rash. This is particularly relevant if these lesions do not resolve with steroid treatment. In such patients, in order to prevent a misdiagnosis of bullous pemphigoid, scrapings for Sarcoptes Scabiei mites and eggs should be taken.

A novel dehydroepiandrosterone analog improves functional recovery in a rat traumatic brain injury model.

The purpose of this study was to investigate the efficacy of a novel steroid, fluasterone (DHEF, a dehydroepiandrosterone (DHEA) analog), at improving functional recovery in a rat model of traumatic brain injury (TBI). The lateral cortical impact model was utilized in two studies of efficacy and therapeutic window. DHEF was given (25 mg/kg, intraperitoneally) at the initial time point and once a day for 2 more days. Study A included four groups: sham injury, vehicle treated (n = 22); injured, vehicle treated (n = 30); injured, pretreated (5-10 min prior to injury, n = 24); and injured, posttreated (initial dose 30 min postinjury, n = 15). Study B (therapeutic window) included five groups: sham injury, vehicle treated (n = 17); injured, vehicle treated (n = 26); and three posttreatment groups: initial dose at 30 min (n = 18), 2 h (n = 23), or 12 h (n = 16) postinjury. Three criteria were used to grade functional recovery. In study A, DHEF improved beam walk performance both with pretreatment (79%) and 30-min posttreatment group (54%; p < 0.01, Dunnett vs. injured vehicle). In study B, the 12-h posttreatment group showed a 97% improvement in beam walk performance (p < 0.01, Dunnett). The 30-min and 12-h posttreatment groups showed a decreased incidence of falls from the beam, which reached statistical significance (p < 0.05, Dunnett). Tests of memory (Morris water maze) and neurological reflexes both revealed significant improvements in all DHEF treatment groups. In cultured rat mesangial cells, DHEF (and DHEA) potently inhibited interleukin-1beta-induced cyclooxygenase-2 (COX2) mRNA and prostaglandin (PGE2) production. In contrast, DHEF treatment did not alter injury-induced COX2 mRNA levels in the cortex or hippocampus. However, DHEF (and DHEA) relaxed ex vivo bovine middle cerebral artery preparations by about 30%, with an IC(50) approximately 40 microM. This was a direct effect on the vascular smooth muscle, independent of the endothelial cell layer. Fluasterone (DHEF) treatments improved functional recovery in a rat TBI model. Possible mechanisms of action for this novel DHEA analog are discussed. These findings suggest an exciting potential use for this agent in the clinical treatment of traumatic brain injury.

Perspectives of low cost arsenic remediation of drinking water in Pakistan and other countries.

Arsenic concentrations above acceptable standards for drinking water have been detected in many countries and this should therefore is a global issue. The presence of arsenic in subsurface aquifers and drinking water systems is a potentially serious human health hazard. The current population growth in Pakistan and other developing countries will have direct bearing on the water sector for meeting the domestic, industrial and agricultural needs. Pakistan is about to exhaust its available water resources and is on the verge of becoming a water deficit country. Water pollution is a serious menace in Pakistan, as almost 70% of its surface waters as well as its groundwater reserves have contaminated by biological, organic and inorganic pollutants. In some areas of Pakistan, a number of shallow aquifers and tube wells are contaminated with arsenic at levels which are above the recommended USEPA arsenic level of 10 ppb (10 microg L(-1)). Adverse health effects including human mortality from drinking water are well documented and can be attributed to arsenic contamination. The present paper reviews appropriate and low cost methods for the elimination of arsenic from drinking waters. It is recommended that a combination of low cost chemical treatment like ion exchange, filtration and adsorption along with bioremediation may be useful option for arsenic removal from drinking water.

One-year outcomes from the TAXUS express stent versus cypher stent.

We compared 1-year outcomes in patients treated with paclitaxel-eluting stents (PESs) or sirolimus-eluting stents (SESs) in "real-world" clinical practice. Clinical outcomes were evaluated in 1,558 consecutive, unselected, retrospectively collected patients treated with drug-eluting stents (DESs; PES = 816, SES = 742) at 19 United States centers. The primary end point was 1-year target vessel revascularization (TVR). The study included a prespecified diabetic cohort (PES = 289, SES = 247), for which efficacy comparisons between DESs were analyzed according to vessel diameter and presence of chronic kidney disease. Baseline demographic, angiographic, and procedural characteristics were similar between patients treated with PESs and those treated with SESs. At 1 year, there were no overall statistical differences in death, myocardial infarction, TVR, or stent thrombosis. In the diabetic cohort, however, the cumulative incidence of TVR was significantly lower for patients treated with PESs (3%) compared with SESs (9%, p <0.01), which persisted after adjustment for baseline differences (hazard ratio 0.29, 95% confidence interval 0.12 to 0.67). This decrease in TVR with PES was similar in insulin- and noninsulin-requiring diabetic patients. In multivariate analysis, independent predictors of TVR included diabetes, bifurcation stenting, and overlapping stents; in the diabetic cohort, treatment with SESs was also a multivariate predictor of TVR. In conclusion, in this observational, retrospective analysis of DES-treated patients, PESs and SESs demonstrated similar overall safety and efficacy, but PESs were associated with a significant decrease in 1-year TVR rates in diabetic patients.

Cyclooxygenase-2-specific inhibitor improves functional outcomes, provides neuroprotection, and reduces inflammation in a rat model of traumatic brain injury.

OBJECTIVE: Increases in brain cyclooxygenase-2 (COX2) are associated with the central inflammatory response and with delayed neuronal death, events that cause secondary insults after traumatic brain injury. A growing literature supports the benefit of COX2-specific inhibitors in treating brain injuries. METHODS: DFU [5,5-dimethyl-3(3-fluorophenyl)-4(4-methylsulfonyl)phenyl-2(5)H)-furanone] is a third-generation, highly specific COX2 enzyme inhibitor. DFU treatments (1 or 10 mg/kg intraperitoneally, twice daily for 3 d) were initiated either before or after traumatic brain injury in a lateral cortical contusion rat model. RESULTS: DFU treatments initiated 10 minutes before injury or up to 6 hours after injury enhanced functional recovery at 3 days compared with vehicle-treated controls. Significant improvements in neurological reflexes and memory were observed. DFU initiated 10 minutes before injury improved histopathology and altered eicosanoid profiles in the brain. DFU 1 mg/kg reduced the rise in prostaglandin E2 in the brain at 24 hours after injury. DFU 10 mg/kg attenuated injury-induced COX2 immunoreactivity in the cortex (24 and 72 h) and hippocampus (6 and 72 h). This treatment also decreased the total number of activated caspase-3-immunoreactive cells in the injured cortex and hippocampus, significantly reducing the number of activated caspase-3-immunoreactive neurons at 72 hours after injury. DFU 1 mg/kg amplified potentially anti-inflammatory epoxyeicosatrienoic acid levels by more than fourfold in the injured brain. DFU 10 mg/kg protected the levels of 2-arachidonoyl glycerol, a neuroprotective endocannabinoid, in the injured brain. CONCLUSION: These improvements, particularly when treatment began up to 6 hours after injury, suggest exciting neuroprotective potential for COX2 inhibitors in the treatment of traumatic brain injury and support the consideration of Phase I/II clinical trials.