The Role of Osteogenic Effect and Vascular Function in Bone Health in Hypertensive Rats: A Study of Anti-hypertensive and Hemorheologic Drugs.

Vascular dysfunction contributes to the development of osteopenia in hypertensive patients, as decreased blood supply to bones results in tissue damage and dysfunction. The effect of anti-hypertensive medicines on bone mass in hypertensive individuals is inconclusive because of the varied mechanism of their action, and suggests that reducing blood pressure (BP) alone is insufficient to enhance bone mass in hypertension. Pentoxifylline (PTX), a hemorheological drug, improves blood flow by reducing blood viscosity and angiogenesis, also has an osteogenic effect. We hypothesized that improving vascular function is critical to increasing bone mass in hypertension. To test this, we screened various anti-hypertensive drugs for their in vitro osteogenic effect, from which timolol and hydralazine were selected. In adult female spontaneously hypertensive rats (SHRs), timolol and hydralazine did not improve vascular function and bone mass, but PTX improved both. In female SHR animals, PTX restored bone mass, strength and mineralization, up to the level of normotensive control rats. In addition, we observed lower blood vasculature in the femur of adult SHR animals, and PTX restored them. PTX also restored the bone vascular and angiogenesis parameters that had been impaired in OVX SHR compared to sham SHR. This study demonstrates the importance of vascular function in addition to increased bone mass for improving bone health as achieved by PTX without affecting BP, and suggests a promising treatment option for osteoporosis in hypertensive patients, particularly at-risk postmenopausal women.

Anatomical variations in living donors for liver transplantation-prevalence and relationship.

PURPOSE: Living donor liver transplantation (LDLT) is a widely accepted option to address the lack of a deceased liver program for transplantation. Understanding vascular and biliary anatomy and their variants is crucial for successful and safe graft harvesting. Anatomic variations are common, particularly in the right hepatic lobe. To provide evidence for screening potential liver transplant donors, the presence of vascular and biliary anatomic variations in Pakistan's preoperative assessment of transplantation donor candidates was explored. METHODS: This retrospective cross-sectional study evaluated the hepatic artery, portal vein, hepatic vein, and biliary variations in living liver donors. The study included 400 living liver donors; data were collected from March 2019 to March 2023. We used a CT scan and MRCP to assess the anatomical variations. RESULTS: The study examined 400 liver donors aged 18 to 53 years. Conventional arterial anatomy was the most common (65.8%), followed by replaced right hepatic artery (16%) and replaced left hepatic artery (10.8%). Conventional type 1 biliary anatomy was seen in 65.8% of cases. The dominant right hepatic vein was found in 13.3% of donors. There was a significant association between the prevalence of variant portal venous anatomy with variant biliary anatomy. CONCLUSION: Variations of the hepatic arterial, portal venous, and biliary systems are frequent and should be carefully evaluated while selecting a suitable living donor. A strong relationship between variant portal venous and biliary anatomy was found. These findings can aid in selecting suitable candidates and improving surgical planning for liver transplantation.

Mobility, bioaccessibility, pollution assessment and risk characterization of potentially toxic metals in the urban soil of Lahore, Pakistan.

The present study is based on the measurement of potentially toxic metal contents employing various extraction methodologies aimed at the evaluation of their mobility, bioaccessibility and bioavailability in the urban soil (n = 56) of Lahore, Pakistan. Selected metal levels in the soil were quantified using flame atomic absorption spectrometry. On the average basis, aqua regia and glycine extracts revealed comparatively higher contents for most of the metals; average concentrations of Fe, Mn, Zn, Pb, Cu, Cr, Co and Cd were found at 1566, 451.1, 114.8, 52.84, 39.15, 24.82, 12.59 and 3.953 mg/kg in aqua regia extract, while in glycine extract the metal levels were found at 579.6, 174.2, 74.72, 49.74, 19.28, 7.103, 4.692 and 3.357 mg/kg, respectively. However, Cd, Pb, Cu and Zn showed significantly higher mobility and bioavailability in the soil, while Co, Fe and Mn were least mobile/bioavailable. The pollution index was assessed in terms of enrichment factor and modified degree of contamination which revealed severe to significant contamination and anthropogenic enrichment of Cd, Pb, Cu and Zn. Multivariate analysis showed mostly anthropogenic contributions for Zn-Cu-Cr-Pb-Cd. Health risk assessment revealed relatively higher exposure of the metals through ingestion, while only minor contributions were noted for inhalation and dermal contact. Hazard quotient index was within the safe limit (< 1.0) in all soil extractions, thereby indicating no significant non-carcinogenic health risks. The incremental lifetime cancer risk for Cr (4.1E-06) through ingestion was comparatively higher than the safe limit which showed significant lifetime cancer risk to the local population.

Sequential extraction of selected metals to assess their mobility, pollution status and health risk in roadside soil.

Assessment of the mobility and contamination of trace metals in the roadside soil is important to explore the environmental quality and potential risks to the public health. The contents of selected metals (Ca, Mg, Sr, K, Na, Li, Fe, Mn, Zn, Cu, Ag, Co, Ni, Cr, Cd and Pb) in the roadside soil collected from major highways/roadsides of Lahore, Pakistan were quantified employing mBCR sequential extraction. Among the metals, Ca, Sr and Na showed highest contribution in exchangeable fraction, Pb in the reducible fraction and K, Li, Fe, Ag, Ni, Cu and Cr in the residual fraction. However, Mg and Mn exhibited relatively higher contents in exchangeable and residual fractions while Cd, Co and Zn showed relatively higher concentration in all four fractions. Comparatively higher mobility and availability in the soil was shown by Ca followed by Sr, Pb, Na, Cd, Zn, Co, Mn, Cu, Ag and Ni. Principal component analysis demonstrated considerable anthropogenic contributions of the trace metals in the roadside soil. The pollution indices showed that the soil was heavily to extremely polluted by Cd and Ag, followed by significant to very high contamination for Co, Ni and Pb. The modified degree of contamination (4.60 and 3.99 in summer and winter, respectively) revealed an overall high degree of contamination. The health risk assessment revealed that the calculated risks were within the safe limit thereby indicating insignificant non-carcinogenic and carcinogenic heath risk to the populace.

Foreign body aspiration presenting as a chronic lung disease: a unique finding in an elderly patient.

Foreign body aspiration is a serious clinical manifestation in the elderly and has a significant potential to cause life-endangering harm. In this unique report, we highlight the case of a seventy-year-old conscious male, who reported with complaints of chronic cough initially diagnosed as chronic bronchitis; however, on radiological examination, the infectious nidus was identified as a 5 cm long metallic nail in the right lower lung.

Impact of an electronic medical record-based automated screening program for critical congenital heart disease: Emirates Health Services, United Arab Emirates.

BACKGROUND: Almost eight children per 1000 live births are expected to have a congenital heart defect globally. The seven most critical congenital heart conditions that cause severe compromise on the patient's quality and duration of life are collectively referred to as the Critical Congenital Heart Diseases (CCHD). CCHD is a critical condition that requires prompt detection and intervention as a life-saving measure. Pulse oximetry is a non-invasive, highly specific, and moderately sensitive method that can be used for screening new-borns for CCHD. The Emirates Health Services (EHS), UAE, adopted a strategy of developing a stringent program for newborn screening of Critical Congenital Heart disease, which would help in the early diagnosis and treatment of CCHD patients. An automated EMR (Wareed) driven solution was introduced to enhance this program as part of the routine workflow for the nurse care providers. METHODS: Our study is a retrospective observational study that aims to understand: the prevalence of CCHD in our target population and to study the impact of an automated program on screening compliance and its implications for early diagnosis of CCHD. RESULTS: We found that an EMR-driven automated screening program was highly effective in achieving high compliance (98.9%). It created a (statistically significant) improvement in the disease identification for CCHD in live births at EHS facilities. CONCLUSION: We conclude that implementing an automated protocol through the EMR can effectively improve new-born screening coverage. It reduces the days to CCHD diagnosis, which would improve health outcomes in neonates.

Solving the Integral Differential Equations with Delayed Argument by Using the DTM Method.

Recently, a lot of attention has been paid to the field of research connected with the wireless sensor network and industrial internet of things. The solutions found by theorists are next used in practice in such area as smart industries, smart devices, smart home, smart transportation and the like. Therefore, there is a need to look for some new techniques for solving the problems described by means of the appropriate equations, including differential equations, integral equations and integro-differential equations. The object of interests of this paper is the method dedicated for solving some integro-differential equations with a retarded (delayed) argument. The proposed procedure is based on the Taylor differential transformation which enables to transform the given integro-differential equation into a respective system of algebraic (nonlinear, very often) equations. The described method is efficient and relatively simple to use, however a high degree of generality and complexity of problems, defined by means of the discussed equations, makes impossible to obtain a general form of their solution and enforces an individual approach to each equation, which, however, does not diminish the benefits associated with its use.

Environmental regulations, political risk and consumption-based carbon emissions: Evidence from OECD economies.

The staggering rise in global temperature and abrupt change of climate are the responses of nature alerting humanity to limit the emissions of hazardous gases and adopt environmentally-benign life style. The present study explores empirically whether any changes in environmental policy stringency (EPSI), political risk (PR), and the interaction term of EPSI*PR result in any alteration of consumption-based carbon emissions (CBCE) of the 24 advanced OECD economies over the period of 1990-2020. Prior to the empirical estimations, various diagnostic tests are employed. The empirical techniques include, panel cointegration check, Cross-sectional Augmented Autoregressive Distributed Lags (CS-ARDL), and Dumitrescu & Hurlin panel causality test. The findings confirm that imports, gross domestic product, and stringency of environment policies activate CBCE in short-run. Whereas, a unit improvement in political risk and its interaction with environmental policy stringency give rise to 0.231 MtCO2 of CBCE in long run. Interestingly, the squared term of environmental policy stringency effectively tackles such emissions. Based on the findings, we conclude that the present environment related policies of OECD member states does not effectively limit CBCE. In order to achieve genuine emissions reduction goals, the selected nations should restructure their environment related policies by prioritizing increments in environmental policy stringency along with minimizing the risks involved in the political system.

Early suspicion can save lives; mucormycosis in two children with diabetic ketoacidosis in Pakistan.

Mucormycosis is a cause of fulminant necrotising fungal infection in children with underlying immunocompromising conditions. Rhino-orbito-cerebral infection is its most common form in the paediatric group with uncontrolled diabetes mellitus or diabetic ketoacidosis. The initial presentation can mimic a bacterial infection; thus a high index of suspicion is needed for timely intervention to reduce morbidity and mortality. We have presented a case of rhino-orbito-cerebral mucormycosis (ROCM) in two patients with diabetic ketoacidosis for the first time from Pakistan. Both the patients couldnot survive due to extensive disease on late presentation.

A review: Surveillance of lumpy skin disease (LSD) a growing problem in Asia.

Lumpy skin disease (LSD) is a viral disease caused by lumpy skin disease virus (LSDV), a member of Capripoxvirus, genus of Poxviridae family. It is a transboundary infection of monetary significance that primarily affects water buffaloes and cattle. LSD was known to be once endemic in Saharan regions of Africa but later on reported in central Asian and neighboring countries of Pakistan like, India, Iran and China. It is a vector borne disease and arthropods are believed to be the main perpetrators. It is discernible by its high morbidity and low mortality. Characteristic lumps on skin and high fever are considered as major signs while reduced milk production, infertility, early embryonic death and anorexia are some of the salient clinical manifestations of the disease. Additionally, nodules on mucosa of oro-pharynx, udder, genitalia and rectum are usually observed on examination. This article summarizes LSD outbreaks across Asia during last fifteen years. It is a general consensus amongst the veterinary community that disease is endemic in Pakistan as it shares borders with India, Iran and China where recent outbreaks are reported. Historically Pakistan is free of LSD, however it is at high risk of a LSDV outbreak as neighboring regions are becoming endemic. Vaccination, strict quarantine measures, limited movement of livestock along with vector control could be effective for preventing the spread of the disease. This review aims to summarize the latest developments in the epidemiology of LSD with the focus on transboundary spread, possible emergence and economic implications on Pakistan.

Fasciola helminth defense molecule-1 protects against experimental arthritis by inhibiting osteoclast formation and function without modulating the systemic immune response.

An inverse correlation between helminth infection and the autoimmune disease appears to be contributed by the anti-inflammatory factors produced by these organisms. Suppressing osteoclast function without affecting the systemic immunological response is an emerging therapeutic strategy for rheumatoid arthritis (RA). We observed that a synthetic peptide corresponding to 34 amino acids of C-terminal sequence of Fasciola helminth defense molecule-1 (C-FhHDM-1) inhibited RANKL-induced osteoclast formation and lysosomal acidification with an attendant upregulation of sequestome1/p62, a negative regulator of NF-κB expression. C-FhHDM-1 also suppressed RANKL production from osteoblasts. Macrophages are the major inflammatory cells in the joints of RA and C-FhHDM-1 suppressed ICAM-1 (an inflammatory surrogate) expression in these cells. In a murine model of collagen II-induced arthritis (CIA), C-FhHDM-1 improved clinical score, protected against cartilage destruction, and maintained bone mass and bone architecture of joints compared with the CIA group. C-FhHDM-1 suppressed the CIA-induced expression of TNF, IL-17, and IFN-γ in joints but not their serum levels. The peptide also had no effect on the CIA-induced suppression of T regulatory response. We conclude that C-FhHDM-1 has a joint-specific protective effect in experimental arthritis without mitigating systemic inflammation, and thus could become an adjuvant anti-arthritis therapy to prevent RA-induced osteopenia.

Paradigm shift in the surgical training: The era of innovation, simulation and beyond.

This is an era of transformation of surgical education and training. Modern methods of training are being introduced at a rapid pace and are being adopted in surgical practice not only to improve the outcomes and patient satisfaction, but also to provide an opportunity to develop a new well-structured training curriculum by integrating both traditional and modern approaches to teach and learn surgical skills. Various surgical simulators are in use as training aids and are constantly undergoing further refinement and development. To achieve a smooth transition in surgical training to modern methods, a structured programme has to be developed and validated to bridge the gaps in terms of safety, efficiency and ethics during the training process.

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.

HIV and shifting epicenters for COVID-19, an alert for some countries.

Were southern hemisphere countries right to undertake national lockdown during their summer time? Were they right to blindly follow the self-isolation wave that hit European countries in full winter? As a southern hemisphere country like South Africa stands now as the most COVID-19 and HIV affected country in Africa, we use in this paper, recent COVID-19 data to provide a statistical and comparative analysis that may alert southern hemisphere countries entering the winter season. After that, we use a generalized simple mathematical model of HIV-COVID-19 together with graphs, curves and tables to compare the pandemic situation in countries that were once the epicenter of the disease, such as China, Italy, Spain, United Kingdom (UK) and United States of America (USA). We perform stability and bifurcation analysis and show that the model contains a forward and a backward bifurcation under certain conditions. We also study different scenarios of stability/unstability equilibria for the model. The fractional (generalized) COVID-19 model is solved numerically and a predicted prevalence for the COVID-19 is provided. Recall that Brazil and South Africa share number of similar social features like Favellas (Brazil) and Townships (South Africa) with issues like promiscuity, poverty, and where social distanciation is almost impossible to observe. We can now ask the following question: Knowing its HIV situation, is South Africa the next epicenter in weeks to come when winter conditions, proven to be favorable to the spread of the new coronavirus are comfily installed?

Ruptured mycotic reverse saphenous vein graft aneurysm: A late complication of mediastinitis.

Reverse saphenous vein graft aneurysm (RSVGA) is a rare complication that occurs after coronary bypass grafting surgery. Mycotic aneurysm of reverse saphenous vein graft is even more rare. We describe the case of a 76-year-old man who underwent coronary artery bypass grafting 10 years back and had mediastinitis four to five months after surgery. He presented with chest pain in July 2017 and was diagnosed as NSTEMI. Angiography showed left main coronary artery disease (90%) with aneurysm of reverse saphenous vein graft to right posterior descending artery(RPDA). Emergent percutaneous coronary intervention (PCI) of the left main artery was performed as the patient suffered ventricular arrhythmia for which cardiopulmonary resuscitation (CPR) was done. After CPR, haematoma appeared on the left side of the sternum subcutaneously. CT scan of the chest was conducted which showed a pseudoaneurysm measuring 35 mm in the mid-segment of reverse saphenous vein graft (RSVG) to the right posterior descending artery (RPDA) with a surrounding mediastinal haematoma communicating with subcutaneous haematoma, so RSVGA to RPDA was coiled. As blood culture grew candida, antifungal medication was started. When the patient's condition stabilised he was discharged.

Delay between onset of indication and definitive surgery for tracheal trauma.

Tracheal stenosis is rare but a recognized complication after traumatic injury or prolonged intubation. We assessed the time lag between onset of indication for tracheal reconstruction surgery following trauma and actual surgical intervention. We reviewed our operative records for all patients undergoing tracheal reconstruction over the past 10 years. Files were reviewed retrospectively to collect all the relevant data. Surgically all patients were operated via cervical approach. Series 12 cases were identified with an equal split between external trauma and iatrogenic tracheal trauma from prolonged intubation. On, an average patients presented 185 days after initial indication of surgery however there was a wide range of time lag which leads to the importance of early diagnosis of such injuries to reduce delay of definitive management.

Reversal of Osteopenia in Ovariectomized Rats by Pentoxifylline: Evidence of Osteogenic and Osteo-Angiogenic Roles of the Drug.

Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor and is used for the management of intermittent claudication. We tested whether PTX has oral efficacy in stimulating new bone formation. Rat calvarial osteoblasts (RCO) were used to study the effect of PTX on osteoblast differentiation and angiogenesis. Pharmacokinetic and pharmacodynamic studies were carried out in rats to determine an oral dose of PTX. In ovariectomized (OVX) rats with osteopenia, the effect of PTX on various skeletal parameters was studied, and compared with teriparatide. Effect of PTX on angiogenic signaling was studied by immunoblotting and relevant pharmacologic inhibitors. Bone vascularity was measured by intravenous injection of polystyrene fluorospheres followed by in vivo imaging, and angiogenesis was studied in vitro by tubulogenesis of endothelial cells and in vivo by Matrigel plug assay. Effective concentration (EC50) of PTX in RCO was 8.2 nM and plasma PTX level was 7 nM/mL after single oral dosing of 25 mg/kg, which was 1/6th the clinically used dose. At this dose, PTX enhanced bone regeneration at femur osteotomy site and completely restored bone mass, microarchitecture, and strength in OVX rats. Furthermore, PTX increased surface referent bone formation parameters and serum bone formation marker (PINP) without affecting the resorption marker (CTX-1). PTX increased the expression of vascular endothelial growth factor and its receptor in bones and osteoblasts. PTX also increased skeletal vascularity, tubulogenesis of endothelial cells and in vivo angiogenesis. Taken together, our study suggested that PTX at 16% of adult human oral dose completely reversed osteopenia in OVX rats by osteogenic and osteo-angiogenic mechanisms.

Acalabrutinib and its use in treatment of chronic lymphocytic leukemia.

Acalabrutinib received an accelerated US FDA approval for patients with relapsed/refractory mantle cell lymphoma in 2017 and is currently being evaluated in chronic lymphocytic leukemia (CLL). To date, ibrutinib is the only Bruton tyrosine kinase (BTK) inhibitor that's approved for treatment of CLL. Acalabrutinib is a second generation BTK inhibitor that binds covalently to the Cys481 residue on BTK and has half maximal inhibitory concentration (IC50) of 3 nM. In preclinical mouse models, acalabrutinib significantly reduced proliferation of CLL cells. Results of Phase I/II trials revealed overall response rates (ORR) of 96% in treatment-naive, 93% in relapsed/refractory and 76% in ibrutinib intolerant patients with CLL. The most common adverse effects (>20%) were grade 1-2 comprising constitutional symptoms, GI toxicity, rash and myelosuppression. There were limited grade 3 or 4 toxicities, involving syncope, pneumonia, hypertension, atrial fibrillation, neutropenia and thrombocytopenia.

Semilocal convergence theorem for the inverse-free Jarratt method under new Hölder conditions.

Under the new Hölder conditions, we consider the convergence analysis of the inverse-free Jarratt method in Banach space which is used to solve the nonlinear operator equation. We establish a new semilocal convergence theorem for the inverse-free Jarratt method and present an error estimate. Finally, three examples are provided to show the application of the theorem.

Association of cardiovascular risk factors with disease severity in cerebral cavernous malformation type 1 subjects with the common Hispanic mutation.

BACKGROUND: Cerebral cavernous malformations (CCM) are enlarged vascular lesions affecting 0.1-0.5% of the population worldwide and causing hemorrhagic strokes, seizures, and neurological deficits. Familial CCM type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and is characterized by multiple brain lesions whose number and size increase with age. The number of lesions varies widely for unknown reasons, even among carriers of similar ages with the same mutation. The purpose of this study was to investigate whether cardiovascular (CV) risk factors influence potential markers of familial CCM1 disease severity, such as lesion count and history of intracerebral hemorrhage. METHODS: We analyzed baseline data from 185 Hispanic subjects, enrolled in the Brain Vascular Malformation Consortium study between June 2010 and March 2013. All subjects were carriers of the founder Q455X 'Common Hispanic Mutation' (CHM) in the KRIT1 gene, and had a clinical diagnosis of CCM or had an affected first- or second-degree relative with CCM. We performed a cross-sectional study, collecting detailed clinical information of CCM1-CHM subjects and cerebral susceptibility-weighted magnetic resonance imaging to assess lesion count. Linear or logistic regression analysis of log-lesion count or history of intracerebral hemorrhage and CV risk factors (age, gender, obesity, diabetes, hypertension, hyperlipidemia and smoking status) and related quantitative traits (body mass index, glycosylated hemoglobin levels, blood pressure, lipids levels and pack-years of cigarette smoking) was performed accommodating familial clustering. RESULTS: CCM1-CHM subjects were mainly female (63.8%) and symptomatic at presentation (63.2%). Lesion count was highly variable (mean ± SD: 57.7 ± 110.6; range: 0-713); 90% of CCM1-CHM subjects had multiple lesions at enrollment. Age (p < 0.001) was positively correlated with lesion count and male gender (p = 0.035) was associated with a greater number of lesions. Obesity (p = 0.001) and higher body mass index (p = 0.002) were associated with fewer lesions. No association with hypertension was detected, however, systolic blood pressure (p = 0.002) was associated with fewer lesions. No significant association with lesion count was observed for diabetes, hyperlipidemia, smoking status or for related quantitative traits. History of intracerebral hemorrhage was not significantly associated with any CV risk factors, however, we found borderline associations of hemorrhage with obesity (p = 0.062), systolic blood pressure (p = 0.083) and pack-years of cigarette smoking (p = 0.055). After correction for multiple testing, age and obesity remained significantly associated with lesion count in CCM1-CHM subjects. CONCLUSIONS: These results suggest that several CV risk factors explain some of the variability in lesion count in Hispanic CCM1-CHM subjects. Although age, gender, obesity, body mass index and systolic blood pressure may influence familial CCM1 disease severity, further longitudinal studies in larger sample sizes are essential to confirm these findings.