Effects of imidazole derivatives on cellular proliferation and apoptosis in myeloid leukemia.

BACKGROUND: Acute promyelocytic leukemia (APL) is the sub-type of Acute myeloid leukemia (AML) which is described by differentiation block at promyelocytic stage and t(15; 17) translocation with All trans retinoic acid (ATRA) and arsenic trioxide (ATO) as standard treatments. Chronic myeloid leukemia (CML) translocation t (19; 22) causes a rise in granulocytes and their immature precursors in the blood. Different mutations cause resistance to first-line tyrosine kinase therapies in CML. Beside drug resistance, leukemia stem cells (LSC) are critical resources for relapse and resistance in APL and CML. The drug toxicity and resistant profile associated with LSC and current therapeutics of APL and CML necessitate the development of new therapies. Imidazoles are heterocyclic nitrogen compounds with diverse cellular actions. The purpose of this research was to assess the anti-leukemic properties of four novel imidazole derivatives including L-4, L-7, R-35, and R-NIM04. METHODS AND RESULTS: Pharmacological and biochemical approaches were used which showed that all four imidazole derivatives interfere with the NB4 cells proliferation, an APL cell line, while only L-7 exhibit anti-proliferative activity against K562 cells, a CML cell line. The anti-proliferative effect of imidazole derivatives was linked to apoptosis induction. Further real-time polymerase chain reaction (RT-PCR) analysis revealed downregulation of AXL-Receptor Tyrosine Kinase (AXL-RTK) and target genes of Wnt/beta-catenin pathway like c-Myc, Axin2 and EYA3. An additive effect was observed after combinatorial treatment of L-7 with standard drugs ATRA or Imatinib on the proliferation of NB4 and K562 cells respectively which was related to further downregulation of target genes of Wnt/beta catenin pathway. CONCLUSION: Imidazole derivatives significantly reduce proliferation of NB4 and K562 cells by inducing apoptosis, down regulating of AXL-RTK and Wnt/ß-catenin target genes.

Functional priorities of individuals with spinal cord injury: a Saudi Arabian perspective.

CONTEXT/OBJECTIVE: People with spinal cord injury (SCI) are the deciding force behind the rehabilitation program to improve their quality of life (QoL) based on their personal preferences. Here we aimed to determine the preferences perceived most vital by Saudi SCI population to improve their QoL, and explore if these preferences are affected by gender, education, and duration, level, or extent of injury. DESIGN: Participants ranked seven priorities of bodily functions as Rank I-VII with "I" being "Most important," and "VII" being "Least important." SETTING: Inpatient rehabilitation facility. PARTICIPANTS: 120 participants (>18 years of age) of either sex with SCI without polytrauma, acquired brain injury, neurodegenerative disease, and dementia. OUTCOME MEASURES: Ranking scale of seven priorities of bodily functions as Rank I-VII with "I" being "Most important," and "VII" being "Least important." RESULTS: Of 101 individuals (mean age: 35.2 ± 14.8 years) finally included, 70.3% were males, 66.3% had onset of SCI since ≥ 3 years, 48.5% had a complete injury, and 75% had paraplegia. Most (26.7%) participants ranked walking as the first priority followed by hand/arm function (20.8%). Sexual function was the least important priority (39.6%). Hand/arm function was significantly more important for individuals with tetraplegia (p < 0.001). Trunk strength and balance was significantly less important for individuals with complete injury (p = 0.037). Participants with the onset of injury < 3 years and a complete injury reported bladder/bowel function as significantly more important (p = 0.011). Walking was significantly more important for people with incomplete injury and for people with injury duration ≥ 3 years (p = 0.022, p = 0.002 respectively). CONCLUSION: The top priority in our sample of Saudi people with SCI was walking followed by hand/arm function while the least desired function was regaining sexual function. Walking was a prioritized function for people with injury duration ≥ 3 years and people with a complete injury while hand/arm function was highly prioritized by people with tetraplegia.

Diagnostic accuracy of ultrasonography in diagnosis of Carpal Tunnel Syndrome.

Objective: This study aimed to assess the diagnostic accuracy of Ultrasonography, considering nerve conduction study (NCS) as the gold standard diagnostic modality for carpal tunnel syndrome (CTS). Methods: A cross-sectional study was conducted at the Neurology Department of Allied Hospital, Faisalabad from August, 2020 to January, 2021. NCS and Ultrasonography of wrist were performed for diagnosis of CTS. The sensitivity, specificity, predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy (DA) were calculated for the screening test (Ultrasonography of the wrist), taking NCS as the gold standard. Results: The mean age of the study population was 41.53 ± 8.80 years, with female pre-dominance (71.66%). The right hand was involved in 24(40%) patients, left hand was involved in 4(6.66%) patients, and both hands were involved in 32(53.33%) patients. Among 60 patients, ultrasonography diagnosed 56 (TP+FN) as having CTS, confirmed via nerve conduction study. Sensitivity, specificity, NPV, PPV, and DA of Ultrasonography of the wrist for CTS were 92.8%, 75%, 42.8%, 98.1%, and 91.6%, respectively. Conclusion: Based on the sensitivity and specificity, Ultrasonography may assist in diagnosing CTS.

Genetic overview of postaxial polydactyly: Updated classification.

Polydactyly or polydactylism, also known as a hyperdactyly, is a congenital limb defect with various morphologic phenotypes. Apart from physical and functional impairments, the presence of polydactyly is an indication of an underlying syndrome in the newborn. Usually, it follows as an autosomal dominant/recessive inheritance pattern with defects in the limb development's anteroposterior patterning. Although mutations in several genes have been associated with polydactyly; however, the exact underlying cause, pathways, and disease mechanisms are still unexplored, thus making it of multi-factorial origin. Polydactyly is divided into three subtypes; radial, ulnar, and central polydactyly. So far, 11 loci (PAPA1-PAPA11) and seven human genes have been reported to cause non-syndromic postaxial polydactyly in humans, including the ZNF141, GLI3, IQCE, GLI1, FAM92A1, KIAA0825, and DACH1. In this review, we discuss emerging evidences of clinical and molecular characterization of polydactyly types in term of the involvement of newly associated genes and loci for non-syndromic postaxial polydactyly, and how these might impact our understanding of the genetic mechanisms and molecular etiology involved in the cause of polydactyly.

Delayed discharges at a tertiary rehabilitation centre in Saudi Arabia: contributing factors and cost impact.

There are various challenges in discharging hospitalized patients with disabilities. Discharge process for individuals with disabilities is multifactorial and can vary from one health system to another. The current study is aimed to explore the factors contributing to delayed discharges and to determine the number of exceeded bed days and subsequent cost impact at a government rehabilitation facility in Saudi Arabia. This retrospective cohort study was conducted at the Rehabilitation Hospital of King Fahad Medical City, Riyadh. All the 2285 discharges from inpatient rehabilitation from August 2011 to March 2017 were included in the study. Patients with delayed discharge were identified. Information about the diagnosis and reasons for delayed discharge was obtained from the rehabilitation hospital bed utilization data. The cost impact was calculated based on the number of days patients stayed beyond the estimated length of stay for each diagnosis. Of the 2285 discharges, 531 (23.3%) were delayed. The most common clinical conditions of patients with delayed discharge included spinal cord injury (n = 168, 31.6%) and traumatic brain injury (n = 145, 27.3%). The factors that led to delayed discharges were medical complications (n = 352, 66.7%), organizational factors (n = 83, 15.7%), family factors (n = 46, 8.7%), and external factors (n = 46, 8.7%). A total of 21 817 hospital bed days were exceeded, with an approximate estimated cost of 80 million Saudi Arabian Riyals. Early rehabilitation and enhancement of the discharge process may significantly decrease delayed discharge rates. Strategies need to be adapted to identify patients at risk of delayed discharge based on the factors highlighted in this study. Development of long-term care capacity, community services, and optimizing family and social support can promote timely discharge.

Effectiveness of alteplase infusion for the management of prosthetic mitral valve thrombosis in paediatric age group and proposed algorithm.

INTRODUCTION: The incidence of prosthetic valve implantation is increasing in the paediatric population. Prosthetic valve thrombosis leading to obstruction could potentially be a life-threatening complication. There is a debate regarding optimal management of this complication, and there is limited use of thrombolytic therapy in childhood in the setting of valve thrombosis. OBJECTIVE: We aim to share our experience of successfully using fibrinolytic therapy in terms of alteplase for paediatric prosthetic mitral valve thrombosis and to propose a management algorithm. METHODS: This retrospective analysis of the database was conducted at our hospital including patients who underwent thrombolysis (alteplase) for prosthetic mitral valve thrombosis from June, 2011 to June, 2021. A total of 10 patients with 20 attempts of alteplase infusion were found in our record. RESULTS: Alteplase was successful in 19 attempts to relieve valve thrombosis. The safe and effective dose of alteplase was between 0.1 and 0.3 mg/kg/hour. There were no associated major bleeding complications and alteplase was administered either by central or peripheral line. CONCLUSION: Thrombolysis by alteplase infusion was found to be successful in relief of prosthetic mitral valve thrombosis in paediatric population without major bleeding complications.

Magnetic, Electronic, and Optical Studies of Gd-Doped WO3: A First Principle Study.

Tungsten trioxide (WO3) is mainly studied as an electrochromic material and received attention due to N-type oxide-based semiconductors. The magnetic, structural, and optical behavior of pristine WO3 and gadolinium (Gd)-doped WO3 are being investigated using density functional theory. For exchange-correlation potential energy, generalized gradient approximation (GGA+U) is used in our calculations, where U is the Hubbard potential. The estimated bandgap of pure WO3 is 2.5 eV. After the doping of Gd, some states cross the Fermi level, and WO3 acts as a degenerate semiconductor with a 2 eV bandgap. Spin-polarized calculations show that the system is antiferromagnetic in its ground state. The WO3 material is a semiconductor, as there is a bandgap of 2.5 eV between the valence and conduction bands. The Gd-doped WO3's band structure shows few states across the Fermi level, which means that the material is metal or semimetal. After the doping of Gd, WO3 becomes the degenerate semiconductor with a bandgap of 2 eV. The energy difference between ferromagnetic (FM) and antiferromagnetic (AFM) configurations is negative, so the Gd-doped WO3 system is AFM. The pure WO3 is nonmagnetic, where the magnetic moment in the system after doping Gd is 9.5599575 µB.

Knowledge and Attitudes of Rehabilitation Professional Toward Telerehabilitation in Saudi Arabia: A Cross-Sectional Survey.

Background: Continuity of rehabilitation care after completion of a hospital-based rehabilitation program remains a challenge. This is of considerable significance in Saudi Arabia where there is a lack of community-based rehabilitation, which renders the need of telemedicine services. There is lack of data regarding understanding, awareness, and attitudes of rehabilitation professional toward telerehabilitation. This study was aimed to explore Saudi-based rehabilitation professionals' knowledge of telerehabilitation. Materials and Methods: After pilot testing, a survey questionnaire was distributed to 82 rehabilitation professionals working in different regions of Saudi Arabia. The survey included 14 close-ended questions targeting five domains: demographics, telemedicine knowledge, telerehabilitation service knowledge, social acceptance of these services, and risks associated with these services. Descriptive statistics were obtained by analyzing data using Microsoft Excel. Results: In total 46% of the participants were aware of telerehabilitation service technology but did not use it. 69.51% considered both telerehabilitation and community-based rehabilitation as the best service delivery methods. About 43% of participants reported that lack of knowledge about information technology and cost were the main factors that led to their limited use of telerehabilitation systems. The majority of the participants (52.44%) considered breach of confidentiality to be a risk associated with telerehabilitation services. Conclusions: Even though considerable number of the participants considered telerehabilitation as an important service delivery method, most of them are not involved in telerehabilitation. This renders the need of establishing local telerehabilitation guidelines and addressing the barriers pertaining to training, resources, cost, policy making, confidentiality, and perception of patients.

Telerehabilitation Guidelines in Saudi Arabia.

Rehabilitation needs are increasing globally due to population growth, aging population, high survival rates for people with disability, and severe health conditions. In the past few years, new telecommunication-based practices, including various forms of e-rehabilitation have gained attention all over the world, including the Kingdom of Saudi Arabia (KSA). Telerehabilitation is an alternative way of delivering rehabilitation services in which information and communication technologies are used to expedite communication between the health care professional and the patient at a distant location. It can be beneficial to people in rural areas, especially individuals in isolated communities. At present, the COVID-19 pandemic has forced speedy adoption of telerehabilitation due to restricted traditional in-person visits all over the world, including KSA; however, no telerehabilitation guidelines are available in the country. Since specialized rehabilitation services are limited to main cities of the country, the provision of care by reaching out the underserved areas using telemedicine technology is deemed important. These guidelines were established collaboratively by panel of various rehabilitation experts with input from other practitioners in the field and strategic stakeholders. It will facilitate rehabilitation clinicians practicing in KSA providing consultation, counseling, education, assessment, monitoring, therapy, or follow-up to a patient remotely using telemedicine communication technologies. This document includes administrative, clinical, and technical guidelines, which are aimed to standardize telerehabilitation practice across the country. The core principles are based on standards set forth by American Telemedicine Association and are guided by telemedicine policy in KSA. Additionally, ethical considerations of telerehabilitation practice pertinent to Saudi culture and health care system are elaborated as well. This document serves as a general guide for the provision of telerehabilitation services and do not describe a specialty-specific clinical practice guideline.

Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach.

OBJECTIVE: In this study, small molecules possessing tetrahydropyrimidine derivatives have been synthesized having halogenated benzyl derivatives and carboxylate linkage. As previously reported, FDA approved halogenated pyrimidine derivatives prompted us to synthesize novel compounds in order to evaluate their biological potential. METHODOLOGY: Eight pyrimidine derivatives have been synthesized from ethyl acetoacetate, secondary amine, aromatic benzaldehyde by adding catalytic amount of CuCl2·2H2O via solvent less Grindstone multicomponent reagent method. Molecular structure reactivity and virtual screening were performed to check their biological efficacy as an anti-oxidant, anti-cancer and anti-diabetic agent. These studies were supported by in vitro analysis and QSAR studies. RESULTS: After combined experimental and virtual screening 5c, 5g and 5e could serve as lead compounds, having low IC50 and high binding affinity.

Scimitar syndrome: A rare case of recurrent pneumonia.

Scimitar syndrome is a rare, congenital malformation. It is characterized by partial anomalous pulmonary venous connection to inferior vena cava, hypoplastic right lung along with dextroposition of the heart. Depending on the severity of the defect it can present as early as in neonatal period or incidentally later in life. Its incidence is 1-3 per 100,000 patients. We present a case of a two-year-old girl who presented with recurrent fever, cough and was later diagnosed as scimitar syndrome.

The negative effects of anterior cruciate ligament injury during stroke rehabilitation.

Musculoskeletal problems are commonly reported after stroke resulting in abnormal gait biomechanics, pain, and limitation in performing activities of daily living. Anterior circulate ligament is the most frequently injured knee ligament accounting for approximately 50% of all ligament injuries; however, post stroke anterior cruciate ligament injury is rarely reported. We present a case of a 58-year-old female admitted for inpatient stoke rehabilitation after a left middle cerebral artery stroke. After gaining considerable functional recovery, she was planned to be discharged in two weeks' time when she tripped resulting in a torn anterior cruciate ligament on the hemiperetic side. This resulted in increase in the length of stay and loss of functional gains. We discuss the possible mechanisms and the management plan. Patients with stroke should be monitored for musculoskeletal complications and preventive strategies should be devised to protect from possible ligamentous injuries of the knees.

Comparison of topical capsaicin and topical turpentine Oil for treatment of painful diabetic neuropathy.

BACKGROUND: Diabetes Mellitus is a pandemic of the modern era owing to our rapidly deteriorating lifestyle. Painful diabetic neuropathy is one of the costliest and disabling complications of diabetes mellitus. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Topical Capsaicin and Turpentine Oil are found to be effective in treatment of painful diabetic neuropathy. METHODS: Patients of either gender with ages between 18 and 70 years having painful diabetic neuropathy already taking one oral drug for painful neuropathy and treatment for diabetes mellitus and an HbA1C less than 8.5% were included while Pregnant or lactating mothers, patients with chronic liver disease and patients with renal insufficiency (creatinine >3.0 mg/dl) and peripheral arterial disease were excluded from study. Patients were randomly divided into two groups (A & B) using computer generated random number table. Group A was given topical application of capsaicin while Group B was given topical application of commercially available turpentine oil over painful site on feet. RESULTS: 300 patients were equally divided in two groups. The patients in group A had a Visual Analog Pain Score of 7.91±5.10 at baseline and 5.10±1.343 after 3 months of treatment (p-value 0.0001). The patients in group B had a Visual Analog Pain Score of 7.83±1.012 at baseline and 5.20±1.187 after 3 months of treatment (p-value 0.0001). Chi Square test was applied to compare efficacy of both groups. It was noted that 71 (53%) had efficacy in group A and 63 (47%) had efficacy in the group B but the difference was not statistically significant. (p-value=0.399). CONCLUSIONS: It has been concluded that turpentine oil is effective in managing diabetic neuropathic pain similar to capsaicin cream.

The angulation of the septal structures impacts ventricular imbalance in atrioventricular septal defects with a common atrioventricular junction.

OBJECTIVE: Multiplanar re-formatting of full-volume three-dimensional echocardiography data sets offers new insights into the morphology of atrioventricular septal defects. We hypothesised that distortion of the alignment between the atrial and ventricular septums results in imbalanced venous return to the ventricles, with consequent proportional ventricular hypoplasia. METHODS: A single observer evaluated 31 patients, with a mean age of 52.09 months, standard deviation of 55, and with a range from 2 to 264 months, with atrioventricular septal defects, of whom 17 were boys. Ventricular imbalance, observed in nine patients, was determined by two-dimensional assessment, and confirmed at surgical inspection in selected cases when a univentricular strategy was undertaken. Offline analysis using multiplanar re-formatting was performed. A line was drawn though the length of the ventricular septum and a second line along the plane of the atrial septum, taking the angle between these two lines as the atrioventricular septal angle. We compared the angle between 22 patients with adequately sized ventricles, and those with ventricular imbalance undergoing univentricular repair. RESULTS: In the 22 patients undergoing biventricular repair, the septal angle was 0 in 14 patients; the other eight patients having angles ranging from 1 to 36, with a mean angle of 7.4°, and standard deviation of 11.1°.The mean angle in the nine patients with ventricle imbalance was 28.6°, with a standard deviation of 3.04°, and with a range from 26 to 35°. Of those undergoing univentricular repair, two patients died, with angles of 26 and 30°, respectively. CONCLUSIONS: The atrioventricular septal angle derived via multiplanar formatting gives important information regarding the degree of ventricular hypoplasia and imbalance. When this angle is above 25°, patients are likely to have ventricular imbalance requiring univentricular repair.

FCPS training in the specialty of Physical Medicine and Rehabilitation for physicians in Pakistan: The option less known.

There has been a growing demand for rehabilitation services in Pakistan in recent years, likely due to increasing prevalence of disability. Physical Medicine and Rehabilitation (PM&R) is a branch of medicine which deals with the prevention, diagnosis, and treatment of functional impairments resulting from neuro-musculoskeletal disorders. Physiatrists are physicians who specialize in the specialty of PM&R. College of Physicians and Surgeons of Pakistan started FCPS training in PM&R in the late 1990s. There are various training institutes within and outside Pakistan which are accredited for FCPS training in PM&R. There is a huge vacuum in this specialty in the country likely due to lack of awareness among health care providers. It is considered to be the specialty of the future due to its rapid growth potential, opportunities for sub specializations and unique skills.

From the year 2050; a glimpse of medical education in the future.

This article is supposedly sent from the future; the year 2050.The author describes the evolution of medical education in 21st century and focuses on the challenges ahead of today. The long years of laborious medical education and complex irrelevant curriculum would instigate a loud debate to amend the current educational system. Gradually, the health system would plateau, as rapid turn out of voluminous new information would not be efficiently channelized to actual patient care. Patient dissatisfaction would increase and the clinician-researcher model of physician would be dubious. Consequently, substantial revisions would be inevitable. By year 2050, the author hypothesizes that the system of continuing medical education would be replaced by continuing professional development. The number of years to be a full certified specialist would be significantly shortened and clinicians would be trained to work in a highly specialized multidisciplinary framework. After a common core medical curriculum, health care professionals would adapt different tracks to be physicians, allied health workers and medical scientists. Programme designs would allow early hands on experience in a patient-specialist programme. The main outcomes of patient management would not be limited to diagnosis or treatment of ailment, and would fundamentally incorporate quality of life issues. An early commitment to medical specialty would enable clinicians to focus on their specialized domains, master their skills at the best learning age and retain their energies for tomorrow.

Number of Pakistani physicians working abroad; do we really need to know?

There are around 175,600 registered doctors in Pakistan, but limited data is available about Pakistani physicians pursuing medical careers abroad. Additionally, no data is reported about Pakistani physicians who leave the country to pursue medical career overseas, but end up in non-medical professions. We identified two groups of physicians leaving the country: those going abroad for postgraduate training and residency; and those doing so for better career incentives and monetary benefits and to avoid the deteriorating law and order situation and rising hostilities towards doctors in the last few years. Other factors contributing towards physician's migration include poor service structure and career prospects, lack of research funding, increased workload and stressful work environment. Optimal measures need to be taken so that the locally trained doctors can deliver their services where they are needed the most, instead of seeking overseas opportunities. Similarly, volume of expertise may be enhanced by promoting social accountability among Pakistani physicians working abroad and by creating comparable opportunities within the country.

Insights from the COVID-19 perspective on the necessity of corporate social responsibility in times of crisis in the context of Pakistan.

In light of the COVID-19 pandemic, there has been a notable increase in global awareness among businesses and consumers regarding environmental preservation and health concerns. The degree to which individuals identify with an organization is influenced by the appeal of its organizational identity, which aids in fulfilling important self-definitional needs. Nevertheless, there remains a limited understanding regarding the underlying factors that contribute to the phenomenon of firm identity attraction (IA) within the framework of consumer-business interactions. This study presents a validated framework that examines the antecedents of identity attraction, with COVID-19 being considered as a moderator. The framework is developed based on established theories of social identity and organizational identification. The study in Pakistan's cities utilized a questionnaire survey as its primary research method, while the findings were evaluated through the application of structural equation modelling. The results of our study indicate that the impact of corporate social responsibility (CSR) on firm Identity Attraction (IA) is significantly more pronounced. Although the impact of COVID-19 on the intention to purchase remains unaffected, it does play a favorable role in moderating the influence of CSR on the attraction towards brand.

Rapid fabrication of polyoxometalate-enhanced photo responsive films from ethyl cellulose (EC) and polyvinylpyrrolidone (PVP).

Ethyl cellulose (EC), polyvinylpyrrolidone (PVP), and phosphomolybdic acid (PMoA) were the components of a new photochromic hybrid film composed of heteropoly acids (abbreviated EC-PVP/PMoA), created by solvent evaporation. The EC-PVP/PMoA mechanism, visible light photochromic behaviors, and microstructure were closely studied by transmission electron microscopy (TEM), atomic force microscopy (AFM), ultraviolet-visible (UV-visible) spectroscopy, X-ray photo electronics (XPS), and Fourier transmission infrared spectroscopy (FTIR). FTIR spectra show that neither the core structures of EC, PVP, nor the Keggin structure of PMoA in the EC-PVP/PMoA composite hybrid film were damaged during fabrication. In the presence of oxygen, the yellowish transparent hybrid film exhibited reversible photochromism and significant photochromic reactivity, becoming blue in the presence of visible light. Upon heating the film at 90 °C for 1 h its photoresponsive properties were enhanced, making the blue color more vibrant and stable due to polyethylene glycol (PEG). The XPS spectra demonstrated a proton transfer procedure during the photochromic process, and the presence of Mo+5 species indicated a photoreduction interaction between the PMoA particles and the EC-PVP matrix. To the best of our knowledge, this is the first EC-PVP combined hybrid film with POMs with promising prospects for solar UV detection and smart glass windows applications.