α-Amino bisphosphonate triazoles serve as GGDPS inhibitors.

Depletion of cellular levels of geranylgeranyl diphosphate by inhibition of the enzyme geranylgeranyl diphosphate synthase (GGDPS) is a potential strategy for disruption of protein transport by limiting the geranylgeranylation of the Rab proteins that regulate intracellular trafficking. As such, there is interest in the development of GGDPS inhibitors for the treatment of malignancies characterized by abnormal protein production, including multiple myeloma. Our previous work has explored the structure-function relationship of a series of isoprenoid triazole bisphosphonate-based GGDPS inhibitors, with modifications having impact on enzymatic, cellular and in vivo activities. We have synthesized a new series of α-amino bisphosphonates to understand the impact of modifying the alpha position with a moiety that is potentially linkable to other agents. Bioassays evaluating the enzymatic and cellular activities of these compounds demonstrate that incorporation of the α-amino group affords compounds with GGDPS inhibitory activity which is modulated by isoprenoid tail chain length and olefin stereochemistry. These studies provide further insight into the complexity of the structure-function relationship and will enable future efforts focused on tumor-specific drug delivery.

Burnout among Dental Students of Private and Public Dental Colleges in Pakistan - A Cross-Sectional Study

ABSTRACT Objective: To assess the prevalence of burnout among dental students of public and private institutions in Khyber Pakhtunkhwa and Punjab, Pakistan. Material and Methods: A cross-sectional descriptive survey was conducted at five public and private dental institutions from June 2021 to May 2022. A validated twelve-item closed-ended Burnout Clinical Subtype Questionnaire was distributed among the dental students of two private and two public institutes in Pakistan. The research questions focused on demographic information and students' academic experiences. Data analysis is presented through tables and descriptive methods. Results: A total of 274 dental undergraduate students - second (42.3%), third (35.4%), and final (22.3%) academic year participated in this study. The mean age of the respondents was 21.9, with the range of 20-26 years. Most participants were females (74.1%) compared to the males (25.9%). The findings for burnout syndrome among dentistry students and students in the private and public sectors were not significant. Conclusion: In the current study, burnout levels among dental undergraduates, both private and public, were low.

A quantum mechanical investigation of nanocone oxide as a drug carrier for zidovudine: AIDS drug.

Traditionally, nanocones as a drug delivery material allow controlled drug delivery close to the target area while reducing the toxicity and generic accumulation associated with traditional intravenous injection methods. In the current study, density functional theory (DFT) is employed to investigate the therapeutic potential of carbon nanocone oxide (ONC) as a carrier with zidovudine drug for the treatment of human immunodeficiency virus (HIV). The electronic ground state and excited state were studied to evaluate the drug carrier potential of ONC and Zidovudine-ONC complex. The Frontier Molecular Orbitals (FMOs) and Molecular Electrostatic Potential (MEPs) revealed that the ONC carrier acts as a donor and zidovudine as an acceptor. The FMOs confirmed the interaction between drug and carrier stabilization energy by calculating chemical hardness, material softness, electronegativity, Ionization energy and electron affinity. The natural bond analysis (NBO), non-covalent interaction (NCI) and electron localization function (ELF) revealed the charge transfer between zidovudine and ONC. The density of state (DOS) and Charge Deposition analysis (CDA) provided the charge transfer. To study the excited state of zidovudine, transition density matrix (TDM), UV(Ultra-visible), IR (infrared), Raman, and NMR (Nuclear Magnetic Resonance) spectra of ONC and zidovudine-ONC complex have been plotted. The spectra showed a significant red shift in the zidovudine-ONC complex. Photoinduced electron studies (PET) showed fluorescence quenching because of the interaction between the drug and the carrier and provided a graphical explanation of the distinct excited state. All the results show that the ONC carrier has therapeutic potential as a zidovudine carrier for the treatment of Human Immunodeficiency Virus (HIV).

Synthesis and Characterization of a Tertiary Composite of Cu, Mn, and g-C3N4: An Efficient Visible Light-Active Catalyst for Wastewater Treatment.

In this study, a tertiary composite of graphitic carbon nitride (GCN) with copper and manganese is utilized for photocatalytic degradation to add to efforts for tackling environmental pollution problems. The photocatalytic efficiency of GCN is enhanced with the doping of copper and manganese. This composite is prepared using melamine thermal self-condensation. The formation and characteristics of the composite Cu-Mn-doped GCN are affirmed by X-ray diffraction (XRD), scanning electron microscopy (SEM), ultraviolet (UV), and Fourier transform infrared spectroscopy (FTIR). This composite has been used for the degradation of an organic dye (methylene blue (MB)) from water at neutral conditions (pH = 7) of the solution. The percentage photocatalytic degradation of MB by Cu-Mn-doped GCN is higher than that of Cu-GCN and GCN. The prepared composite enhances the degradation of methylene blue (MB) from 5 to 98% under sunlight. The photocatalytic degradation is enhanced owing to the reduction of hole-electron recombination in GCN, enhanced surface area, and extended sunlight utilization by the doped Cu and Mn.

Host-guest coupling to potentially increase the bio-accessibility of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea by nanocarrier graphyne for brain tumor therapy, a comprehensive quantum mechanics study.

This study aimed to explore the potential of Host-Guest coupling with Nanocarrier graphyne (GPH) to enhance the bioavailability of the drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (LUM) for brain tumor therapy. The electronic, geometric, and excited-state properties of GPH, LUM, and the graphyne@1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea-complex (GPH@LUM-complex) were studied using DFT B3LYP/6-31G** level of theory. The results showed that the GPH@LUM-complex was stable with negative adsorption energy (-0.20 eV), and there was good interaction between GPH and LUM in the solvent phase. The weak interaction forces between the two indicated an easy release of the drug at the target site. The Frontier Molecular Orbitals (FMO), Charge Density Analysis (CDA), and Natural Bond Orbital (NBO) analysis supported LUM to GPH charge transfer during complex formation, and the Reduced Density Gradient (RDG) isosurfaces identified steric effects and non-bonded interactions. UV-visible examination showed the potential of the GPH@LUM-complex as a drug carrier with a blue shift of 23 nm wavelength in the electronic spectra. The PET process analysis revealed a fluorescence-quenching process, facilitating systematic drug delivery. The study concluded that GPH had potential as a carrier for delivering LUM, and different 2D nanomaterials could be explored for drug delivery applications. The theoretical study's findings may motivate researchers to investigate the practical applications of GPH@LUM-complex in oncology.

Patient-reported outcomes and patient-reported outcome measures in liver transplantation: a scoping review.

INTRODUCTION: Generic or condition-specific Patient-reported Outcome Measures (PROMs) are used to measure physical, mental, and social aspects of health to promote patient-centered care. This scoping review aims to identify and summarize generic and condition-specific PRO domains and PROMs that have been assessed and used in liver transplant (LT) candidates and recipients. METHODS: We searched Medline, Embase, Cochrane Database of Systematic Reviews and Register of Trials, PsychInfo, and CINAHL from inception to 08/26/2020. Included studies addressed a PRO or PROM in LT candidates or recipients. RESULTS: After screening, 341 studies yielded 189 unique PRO domains. Mental health domains (depression, anxiety, and guilt) were most frequently assessed, followed by domains of physical and social health. Fifty-one generic and three condition-specific unique PROMs were identified, with only 13% (n = 45) of studies including condition-specific tools. DISCUSSION: The most frequent PROMs were the SF-36, Nottingham Health Profile, Hospital Anxiety and Depression Scale, followed by the Liver Disease Quality of Life (LDQoL). Very few studies used transplant-specific PROMs, which may partly be related to the scarcity of LT-specific instruments. We will use these results in future qualitative research to identify PROs and PROMs to build an electronic PROM toolkit to facilitate patient-centered LT care.

Remarkable non-linear optical properties of gold cluster doped graphyne (GY): A DFT study.

The nonlinear optical (NLO) properties of gold (Au) doped graphyne (GY) complexes are the subject of this quantum mechanical investigation. Detailed profiling of GY@Aucenter, GY@Auside, GY@2Auabove,GY@2Auperpendicular, and GY@3Aucenter is accomplished at CAM-B3LYP/LANL2DZ. The differential influence of various GY based complexes on molecular geometry, vertical ionization energy (VIE), interaction energy (Eint), frontier molecular orbitals (FMOs), density of states (DOS), absorption maximum (λmax), molecular electrostatic potential (MEP), electron density distribution map (EDDM), transition density matrix (TDM), dipole moment (µ) and non-linear optical (NLO) properties have been investigated. Non-covalent interaction (NCI) analysis has been done to explore the sort of interactions in designed complexes. The vibrational frequencies are probed via infrared (IR) analysis. Doping tactics in all complexes dramatically changed charge carrier properties, such as shrinking band gap (Eg) and increasing λmax in the range of 3.97-5.58 eV and 288-562 nm respectively, compared to pure GY with 5.78 eV Eg and 265 nm λmax. When compared to GY (αO = 281.54 andßO = 0.21 au), GY@3Aucenter exhibited a significant increase in static mean polarizability (αO = 415 au) and the mean first hyperpolarizability (ßo = 3652 au) attributable to its lowest excitation energy (ΔE). GY doping has been discovered to be advantageous for designing potential nanoscale devices by focusing on the symphony between small Au clusters and GY and their impacts on NLO aspects.

Controlled supramolecular interaction to enhance the bioavailability of hesperetin to targeted cancer cells through graphyne: a comprehensive in silico study.

In the current study, the drug carrier efficiency of graphyne (GRP) for the transfer of the hesperetin (HPT) drug is evaluated for the first time. The GRP efficacy as a carrier is investigated using the density functional theory (DFT) technique to calculate various physiochemical characteristics such as dipole moment, bandgap, and chemical reactivity-descriptors for HPT, GRP and HPT@GRP complex. The non-covalent-interaction (NCI) plot indicated that GRP and HPT have weak interaction force, which is fundamental for the drug's noticeable offloading from the GRP carrier at its target location. According to frontier molecular orbital analysis, the highest occupied molecular orbital (HOMO) of HPT distributes the charge to the GRP, the lowest unoccupied molecular orbital (LUMO) during excitation. Charge transfer is further supported by charge-decomposition-analysis, which interprets the extensive overlap between HPT and GRP orbitals. In the case of the gas phase, the λ max of the HPT@GRP-complex is redshifted by 9 nm from GRP. In the solvent phase, the λ max value is also redshifted. These theoretically calculated spectra also match experimentally observed spectra rather well. The PET (photoinduced electron-transfer) method and electron-hole theory were used for the graphical explication of distinct excited states. The photoinduced electron transfer (PET) mechanism interprets fluorescence dimming because of interaction. Furthermore, GRP with cationic (+1) and anionic (-1) charge states (GRP+1/-1) showed minor structural disfigurement and formed stable HPT complexes. In the current study, HRP is loading and unloading on GRP very effectively, that can potentially be used in the oncology field. Due to this theoretical study, researchers will be interested in looking at other 2D nanomaterials for drug delivery applications.

Silver cluster doped graphyne (GY) with outstanding non-linear optical properties.

This research study addresses the computational simulations of optical and nonlinear optical (NLO) characteristics of silver (Ag) cluster doped graphyne (GY) complexes. By precisely following DFT and TD-DFT hypothetical computations, in-depth characterization of GY@Agcenter, GY@Agside, GY@2Agperpendicular, GY@2Agabove, and GY@3Agcenter is accomplished using CAM-B3LYP/LANL2DZ while the CAM-B3LYP/mixed basis set is used for study of 2GY@Agcenter, 2GY@Agside, 2GY@2Agperpendicular, 2GY@2Agabove, and 2GY@3Agcenter. The effects of various graphyne surface based complexes on hyperpolarizabilities, frontier molecular orbitals (FMOs), density of states (DOS), absorption maximum (λ max), binding energy (E b), dipole moment (µ), electron density distribution map (EDDM), transition density matrix (TDM), electrostatic potential (ESP), vertical ionization energy (E VI) and electrical conductivity (σ) have been investigated. Infrared (IR), non-covalent interaction (NCI) analysis accompanied by isosurface are performed to study the vibrational frequencies and type of interaction. Doping strategies in all complexes impressively reformed charge transfer characteristics such as narrowing band gap (E g) in the range of 2.58-4.73 eV and enhanced λ max lying in the range of 368-536 nm as compared to pure GY with 5.78 eV E g and 265 nm λ max for (GY@Agcenter-GY@3Agcenter). In the case of (2GY@Agcenter-2GY@3Agcenter), when compared to 2GY with 5.58 eV E g and 275 nm absorption, maximum doping techniques have more effectively modified λ max in the region of 400-548 nm and E g, which is in the order of 2.55-4.62 eV. GY@3Agcenter and 2GY@3Agcenter reflected a noteworthy increment in linear polarizability α O (436.90 au) and (586 au) and the first hyperpolarizability ß O (5048.77 au) and (17 270 au) because of their lowest excitation energy (ΔE) when studied in comparison with GY (α O = 281.54 and ß O = 0.21 au) and 2GY surface (α O = 416 and ß O = 0.06 au). Focusing on harmony between the tiny Ag clusters and graphyne surface as well as their influences on NLO properties, graphyne doping using its two-unit cells (2GY) is found to be expedient for the development of future nanoscale devices.

Previous Infection Combined with Vaccination Produces Neutralizing Antibodies With Potency Against SARS-CoV-2 Variants

SARS-CoV-2 continues to evolve in humans. Spike protein mutations increase transmission and potentially evade antibodies raised against the original sequence used in current vaccines. Our evaluation of serum neutralizing activity in both persons soon after SARS-CoV-2 infection (in April 2020 or earlier) or vaccination without prior infection confirmed that common spike mutations can reduce antibody antiviral activity. However, when the persons with prior infection were subsequently vaccinated, their antibodies attained an apparent biologic ceiling of neutralizing potency against all tested variants, equivalent to the original spike sequence. These findings indicate that additional antigenic exposure further improves antibody efficacy against variants. LAY SUMMARYAs SARS-CoV-2 evolves to become better suited for circulating in humans, mutations have occurred in the spike protein it uses for attaching to cells it infects. Protective antibodies from prior infection or vaccination target the spike protein to interfere with its function. These mutations can reduce the efficacy of antibodies generated against the original spike sequence, raising concerns for re-infections and vaccine failures, because current vaccines contain the original sequence. In this study we tested antibodies from people infected early in the pandemic (before spike variants started circulating) or people who were vaccinated without prior infection. We confirmed that some mutations reduce the ability of antibodies to neutralize the spike protein, whether the antibodies were from past infection or vaccination. Upon retesting the previously infected persons after vaccination, their antibodies gained the same ability to neutralize mutated spike as the original spike, suggesting that the combination of infection and vaccination drove the production of enhanced antibodies to reach a maximal level of potency. Whether this can be accomplished by vaccination alone remains to be determined, but the results suggest that booster vaccinations may help improve efficacy against spike variants.

Tuning the optoelectronic properties of oligothienyl silane derivatives and their photovoltaic properties.

Four new Donor-Acceptor (D-A) type oligothiophenes based structures (C1-C4) were designed by substituting different acceptors moieties around tetrahedral silicon core to simulate their photovoltaic properties. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) quantum analysis were carried out to reconnoiter various parameters of solar cells. A comparative analysis has conducted between designed structures and reference molecule R to conclude our simulated results. Among all the structures, C2 has displayed highest absorption values (380 nm) with red shift and minimum band gap (ΔH-L) of 4.11 eV in dichloromethane at DFT-CAM-B3LYP/6-31G (d,p) using IEFPCM model. The C2 has also shown the lowest values of electron reorganization energy (λe = 0.018eV) and hole reorganization energy (λh = 0.015eV) therefore, could be suggested for use in organic solar cells because of its most noteworthy charge carrier mobilities. Again, C2 has the different trend in TDM graph because the electron density is present in the lower right part of core unit and in the acceptor moiety due to high electron affinities of end capped acceptor having cyanide groups.

Outcome of COVID-19 with co-existing surgical emergencies in children: our initial experiences and recommendations

BackgroundCOVID-19 has changed the practice of surgery vividly all over the world. Pediatric surgery is not an exception. Prioritization protocols allowing us to provide emergency surgical care to the children in need while controlling the pandemic spread. The aim of this study is to share our experiences with the outcome of children with COVID-19 who had a co-existing surgical emergency. MethodsThis is a retrospective observational study. We reviewed the epidemiological, clinical, and laboratory data of all patients admitted in our surgery department through the emergency department and later diagnosed to have COVID-19 by RT-PCR. The study duration was 3 months (April 2020 - June 2020). A nasopharyngeal swab was taken from all patients irrespective of symptoms to detect SARS CoV 2 by RT-PCR with the purpose of detecting asymptomatic patients and patients with atypical symptoms. Emergency surgical services were provided immediately without delay and patients with positive test results were isolated according to the hospital protocol. We divided the test positive patients into 4 age groups for the convenience of data analysis. Data were retrieved from hospital records and analyzed using SPSS (version 25) software. Ethical permission was taken from the hospital ethical review board. ResultsTotal patients were 32. Seven (21.9%) of them were neonates. Twenty-four (75%) patients were male. The predominant diagnosis was acute abdomen followed by infantile hypertrophic pyloric stenosis (IHPS), myelomeningocele, and intussusception. Only two patients had mild respiratory symptoms (dry cough). Fever was present in 13 (40.6%) patients. Fourteen (43.8%) patients required surgical treatment. The mean duration of hospital stay was 5.5 days. One neonate with ARM died in the post-operative ward due to cardiac arrest. No patient had hypoxemia or organ failure. Seven health care workers (5.51%) including doctors & nurses got infected with SARS Co V2 during this period. ConclusionOur study has revealed a milder course of COVID-19 in children with minimal infectivity even when present in association with emergency surgical conditions. This might encourage a gradual restart to mitigate the impact of COVID-19 on childrens surgery.

Conference Report on First Certificate Course in Health Professions Educationat College of Medicine, University of Kerbala, Iraq.(September 2019).

The current status of medical education in Iraq requires complete transformation to conform to the latest trends of modern education. Presently it is compromised due to the influence of political factors, finances, weakness or fragility of planning and security. It has to be re-shaped for the future of medical education to produce good and efficient medical professionals. It is necessary to reform and revise the curriculum as accreditation in accordance with international medical universities. The initial requirement is faculty development in areas including but not limited to, curriculum development, teaching and learning improvement, research capacity building, and leadership development. The capacity building of faculty at College of Medicine, University of Kerbala (CMUCK) has been initiated in collaboration with Medics International at a local and the government level. Medics International conducted the current Course on Certificate in Health Professions Education (CHPE) programme in September, 2019 to facilitate the faculty to revise their curriculum and improve their current educational practices. Further steps will be taken to develop the faculty for Masters in Medical Education (MME), PhD, and fellowship programmes. To face the on-going challenges in the medical and health care system, continous efforts are required for faculty education. Medics International has volunteered to begin a series of Webinars through its global faculty to reach out to the Iraqi Board followed by engagement of the Arab Board covering 18 countries.

Organ donation and transplant: The Islamic perspective.

Islam is the second most practiced religion globally, and the number of Muslims in Western countries has been increasing due to recent trends in migration. Studies have shown that Muslims in the Western world have more negative attitudes toward organ donation and transplantation compared with individuals from other religious backgrounds. Multiple barriers have been postulated that may prevent Muslims from exploring organ donation or transplantation. We conducted a literature review with the goal of summarizing the opinions of major Sunni and Shia scholars and Islamic bodies about organ donation and transplantation, including their opinions and rulings on the neurological determination of death to inform healthcare professionals, community members, and leaders. We also identified factors and attitudes that may prevent members of the Muslim community from achieving equitable access to transplantation or from consenting to donate organs during life or after death. Key factors or concerns identified included: lack of information regarding organ donation, mistrust of the healthcare system, family opinions, sacredness of the body, lack of clear understanding of religious rulings, and opinions of religious leaders. Studies have suggested that partnering with religious leaders to address these concerns may help foster positive attitudes toward organ donation and transplantation.

Quality of Life Is Improved in Renal Transplant Recipients Versus That Shown in Patients With Chronic Kidney Disease With or Without Dialysis.

OBJECTIVES: Health-related quality of life is increasingly used as an important measurement of treatment outcome. Here, quality of life parameters in renal transplant recipients were evaluated and compared with patients with chronic kidney disease on maintenance hemodialysis and with those who were not on dialysis. MATERIALS AND METHODS: This cross-sectional study included patients seen at a number of tertiary renal care hospitals (there were 15 renal transplant recipients, 20 patients on maintenance hemodialysis, and 28 patients with chronic kidney disease not on dialysis). Forty healthy individual were also included as the control group. Different biochemical parameters were analyzed. Quality of life was assessed with the KDQOL-SF-36 (version 1.3) questionnaire. RESULTS: Mean age was 39 ± 11 for transplant patients, 43 ± 11 years for patients on hemodialysis, 49 ± 12 years for patients with chronic kidney disease not on dialysis, and 34 ± 11 years for the healthy control group. Distribution of sex was similar. Transplant recipients had higher quality of life scores, with some scores similar to healthy controls patients, like physical function (P = .85) and social function (P = .25). Scores were 100 ± 12, 69 ± 27, 37 ± 28, and 91 ± 10 (P < .001) for physical function; 94 ± 12, 44 ± 17, 30 ± 14, and 69 ± 29 (P < .001) for pain; 99 ± 11, 61 ± 46, 24 ± 15, and 70 ± 28 (P < .001) for social function; and 91 ± 11, 51 ± 13, 40 ± 7, and 66 ± 11 (P < .001) for energy/fatigue in healthy control, chronic kidney disease patients not on dialysis, hemodialysis patients, and transplant recipients, respectively. CONCLUSIONS: Quality of life is poor in patients with chronic kidney disease. However, renal transplant can improve quality of life. Transplant patients showed many quality of life scores similar to healthy individuals.

Experience Managing Adult Patients on Continuous Ambulatory Peritoneal Dialysis in Bangladesh.

Continuous ambulatory peritoneal dialysis (CAPD) is becoming increasingly known to the patients of Bangladesh, and patient numbers are increasing. Here, we report our experience and clinical outcomes in this field.Our analysis included all CAPD patients managed in a tertiary care hospital in Bangladesh between 2003 and 2015. All patients received a Tenckhoff double-cuff catheter by mini-laparotomy, and twin bags were used in most patients. In acute cases, regular exchanges were started manually with small-volume dwells the same or the next day.During the study period, 500 patients (mean age: 62 ± 18 years; 62% men; 86% percent with diabetes) were managed. Selection of CAPD was made by choice (47%) or for hemodynamic instability (32%), remote residence (17%), or poor vascular access (4%). Total duration of follow-up was 9364 patient-months (range: 1 - 78 months). The peritonitis rate was 1 episode in 30 patient-months. Fewer than 5% of patients required catheter removal. Similarly, the percentages of catheter tip migration and fluid leak were at the lower end. Patient survival was 68%, 48%, 38%, 22%, and 8% at 1, 2, 3, 5, and 7 years. Deaths were mostly attributable to vascular events.In a population with predominantly diabetic patients, CAPD was shown to be a viable mode of renal replacement therapy. The rates of peritonitis and catheter-related complications were low. Survival in the initial years can be considered acceptable.

Osteoarthritis Increases Paresthestic and Akathisic Pain, Anxiety Case-ness, and Depression Severity in Patients With Parkinson's Disease.

Objective: Parkinson's disease (PD) patients are known to suffer from pain, anxiety, and depression, but the exact degree of association between the two is unknown. As many PD patients also suffer from physical impairments, this cross-sectional case-control study sets out to compare and determine the case-ness of pain, anxiety and depression in PD patients that suffer with or without symptomatic osteoarthritis (OA). The goal of this study, therefore, was to observe if additional pain associated with comorbid OA in PD patients is correlated with greater depression and anxiety rates. The importance of understanding the burden of pain and increased depression severity of PD and OA patients is so that they may be screened appropriately based on the symptoms, which may increase their overall quality of life. Methods:This cross-sectional case-control study included 3 groups of 34 patients and 78 healthy age and gender-matched control participants. PD patients with symptomatic OA (PD+OA), PD patients without symptomatic OA (PD), patients with symptomatic OA but no PD (OA), and healthy control participants (Control). A PD patient group with Restless Legs Syndrome (PD+RLS) of 27 patients was also included. All participants completed questionnaires to assess for pain, depression, and anxiety. Results:PD+OA and PD patients had worsened depression severity and were more likely to report anxiety and depression case-ness than OA patients. PD+OA patients were more likely to complain about paresthestic and akasthisic pain, but less likely to complain about aching pain compared to PD patients and OA patients. PD+OA patients were more likely to have greater pain severity, and were more likely to report radiating and sharp pain than PD+RLS patients. PD+OA patients were also more likely to report higher depression case-ness than PD+RLS patients. Conclusion:PD with OA seems to be linked with specific pain characteristics (akathisia and paraesthesia) as well as heightened overall pain severity and pain interference in comparison to OA alone, PD alone and PD with RLS. PD is also correlated with depression severity and anxiety case-ness in OA when compared to the OA alone, PD alone and PD with RLS.

Therapeutic management of trypanosomosis with ophthalmic involvement in a dog.

The present report communicates a case of canine trypanosomosis with ophthalmic involvement, its diagnosis, hemato-biochemistry and therapeutic management in a 2 year old dog. The dog had history of bilateral corneal opacity and impaired vision since last 4 weeks. On the basis of history and clinical signs, a presumptive diagnosis of canine trypanosomosis was made followed by confirmation with Giemsa stained buffy coat smear examination. Therapeutic regimen was comprised of Diminazine aceturate @ 3.5 mg/kg deep IM for two occasions 24 h apart along with parenteral fluids, hematinics, NSAID and multivitamins which yielded favourable response by third day post-therapy. Haemato-biochemical parameters took nearly 14 days of time to return to near normal levels. Improvement with respect to corneal opacity took 6 weeks of time and the animal was followed up to 3 months without any recurrence.

Nonsecretory multiple myeloma presenting as an intestinal tumor.

We report a case of a 43-year-old Caucasian man who presented with colicky abdominal pain and microcytic hypochromic anemia. The patient underwent a colonoscopy where a tumor was seen in the ascending colon; histology showed plasmacytoma of the colon. From the protein electrophoresis, no monoclonal band or free light chains were detected nor was urinary Bence Jones protein present. A bone marrow biopsy showed plasma cell myeloma. To the best of our knowledge, this is the first case of nonsecretory multiple myeloma presenting as plasmacytoma of the colon.

Functional analysis of HIV type 1 Nef gene variants from adolescent and adult survivors of perinatal infection.

Throughout the world, infants and children with HIV-1 infection are increasingly surviving into adolescence and adulthood. As HIV Nef is an important determinant of the pathogenic potential of the virus, we examined nef alleles in a cohort of extreme long-term survivors of HIV infection (average age of 16.6 years) to determine if Nef defects might have contributed to patient survival. HIV nef gene sequences were amplified for phylogenetic analysis from 15 adolescents and adults infected by mother-to-child transmission (n=10) or by blood transfusion (n=5). Functional analysis was performed by inserting patient-derived nef sequences into an HIV-derived vector that permits simultaneous evaluation of the impact of the Nef protein on MHC-I and CD4 cell surface expression. We found evidence of extensive nef gene diversity, including changes in known functional domains involved in the downregulation of cell surface MHC-I and CD4. Only 3 of 15 individuals (20%) had nef alleles with a loss of the ability to downregulate either CD4 or MHC-I. Survival into adulthood with HIV infection acquired in infancy is not uniformly linked to loss of function in nef. The Nef protein remains a potential target for immunization or pharmacologic intervention.