Advances in neuroimaging for HIV-1 associated neurological dysfunction: clues to the diagnosis, pathogenesis and therapeutic monitoring

Persons with advanced human immunodeficiency virus type one (HIV-1) infection seek medical advice for a wide range of neurological disorders including, but not limited to, peripheral neuropathy, toxoplasmosis, cryptococcal meningitis, cytomegalovirus retinitis progressive multifocal leukoencephalopathy, lymphoma and dementia. The diagnosis of HIV-1-associated dementia (HAD) induced as a direct consequence of HIV infection of the brain comes commonly by exclusion. Diagnostic decisions can often be clouded by concomitant depression, motor impairments, and lethargy that follow debilitating immune suppression and weight loss. Indeed, cognitive, motor and behavior abnormalities underlie a variety of neurological dysfunctions associated with advanced HIV-1 infection. Thus, even combinations of clinical, laboratory and neuroimaging tests [for example, magnetic resonance imaging (MRI), computed tomography (CT), single photon emission computed tomography (SPECT) and positron emission tomography (PET)] often fail to provide conclusive diagnostic information. Nonetheless, the recent development of quantitative MR spectroscopic imaging has improved diagnostic possibilities for HAD. We are pleased to discuss these developments as well as taking a forward look into what will soon be made available to improve neuroimaging diagnostic precision. New MR and SPECT testing are being developed in our laboratories and elsewhere both for animal model systems and in humans with HIV-1 disease. Such tests can facilitate dynamic measures of HIV-1 neuropathogenesis providing information for disease events that even 2 years ago were unattainable.     

Insulin resistance as a predictor of age-related diseases

The current study was initiated to evaluate the ability of insulin resistance to predict a variety of age-related diseases. Baseline measurements of insulin resistance and related variables were made between 1988-1995 in 208 apparently healthy, nonobese (body mass index < 30 kg/m2) individuals, who were then evaluated 4-11 yr later (mean +/- SEM = 6.3 +/- 0.2 yr) for the appearance of the following age-related diseases: hypertension, coronary heart disease, stroke, cancer, and type 2 diabetes. The effect of insulin resistance on the development of clinical events was evaluated by dividing the study group into tertiles of insulin resistance at baseline and comparing the events in these 3 groups. Clinical endpoints (n = 40) were identified in 37 individuals (18%) of those evaluated, including 12 with hypertension, 3 with hypertension + type 2 diabetes, 9 with cancer, 7 with coronary heart disease, 4 with stroke, and 2 with type 2 diabetes. Twenty-eight out of the total 40 clinical events were seen in 25 individuals (36%) in the most insulin-resistant tertile, with the other 12 occurring in the group with an intermediate degree of insulin resistance. Furthermore, insulin resistance was an independent predictor of all clinical events, using both multiple logistic regression and Cox's proportional hazards analysis. The fact that an age-related clinical event developed in approximately 1 out of 3 healthy individuals in the upper tertile of insulin resistance at baseline, followed for an average of 6 yr, whereas no clinical events were observed in the most insulin-sensitive tertile, should serve as a strong stimulus to further efforts to define the role of insulin resistance in the genesis of age-related diseases.     

Association between high vancomycin minimum inhibitory concentration and clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia - A retrospective cohort study

European Journal of Clinical Microbiology & Infectious Diseases - The purpose of this study is to determine the role of high (≥ 1.5 mg/L) vancomycin minimum inhibitory concentration...     

Correction to: Prenatal attachment: Using measurement invariance to test the validity of comparisons across eight culturally diverse countries

Archives of Women's Mental Health - A Correction to this paper has been published: https://doi.org/10.1007/s00737-021-01122-7     

Needle biopsy findings in prostatic adenocarcinoma: experience at a tertiary care center in a developing country

The objectives of this study are to report the findings in prostatic needle biopsies positive for cancer seen in our practice with regard to the frequency of cancer detected at various sites, the cancer volume, Gleason grade, presence of perineural invasion, and others; to correlate cancer volume with Gleason grade, perineural invasion, and serum prostate-specific antigen (PSA) levels; and to correlate Gleason grade with serum PSA levels. The study was conducted at The Section of Histopathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan. All consecutive needle biopsies received from January 1, 2011 to June 30, 2012, which were positive for prostatic adenocarcinoma, were included in the study. Statistical analysis was carried out using SPSS 19.0 software package (SPSS Hong Kong Headquarters, Quarry Bay, Hong Kong). A total of 97 needle biopsies positive for carcinoma in this period were included. Prostate-specific antigen levels were available in 60.8% cases and ranged from 5.0 to 1747 ng/mL. Tumor was bilaterally present in 54.6% cases. Tumor positivity in right apex, mid, and base was 52.6%, 54.6%, and 51.5%, respectively. Tumor positivity in left apex, mid, and base was 55.7%, 63.9%, and 59.8%, respectively. Average tumor volume in right apex, mid, and base was 51.2%, 50.6%, and 49.9%, respectively. Average tumor volume in left apex, mid, and base was 49.8%, 49.1%, and 51.6%, respectively. Gleason score was 6 in 52.6% cases and 7 in 28.9% cases. Perineural invasion was positive in 46.4% cases. High-grade prostatic intraepithelial neoplasia was seen in 4 (4.1%) of 97 cases. On statistical analysis, no significant correlation was found between tumor volume and serum PSA levels. However, significant correlation was found between tumor volume and Gleason grade and between tumor volume and presence of perineural invasion. No significant correlation was found between Gleason grade and serum PSA level. To our knowledge, these are the first reported findings in prostatic needle biopsies from Pakistan. Most prostatic carcinomas in our country are still diagnosed on transurethral resection specimens, and needle biopsies are quite uncommon. Findings in needle biopsies will help in predicting adverse prognostic factors on radical prostatectomies and in planning surgery accordingly.     

Molecularly imprinted polymeric coatings for sensitive and selective gravimetric detection of artemether

Monitoring antimalarial drugs is necessary for clinical assays, human health, and routine quality control practices in pharmaceutical industries. Herein, we present the development of sensor coatings based on molecularly imprinted polymers (MIPs) combined with quartz crystal microbalance (QCM) for sensitive and selective gravimetric detection of an antimalarial drug: artemether. The MIP coatings are synthesized by using artemether as the template in a poly(methacrylic acid-co-ethylene glycol dimethacrylate) matrix. Artemether-MIP and the non-imprinted polymer (NIP) control or reference layers are deposited on 10 MHz dual-electrode QCM by spin coating (187 ± 9 nm layer thickness after optimization). The coatings are characterized by FTIR spectroscopy and atomic force microscopy that reveal marked differences among the MIP and NIP. The MIP-QCM sensor exhibits high sensitivity (0.51 Hz ppm⁻¹) with sub-10 ppm detection and quantification limits. The MIP-QCM sensor also exhibits a 6-fold higher sensitivity compared to the NIP-QCM, and a dynamic working range of 30–100 ppm. The response time of MIP-QCM devices for a single cycle of analyte adsorption, signal saturation, and MIP regeneration is less than 2.5 min. The sensor also demonstrates selectivity factors of artemether-MIP of 2.2 and 4.1 compared to artemisinin and lumefantrine, respectively. Reversibility tests reveal less than 5% variation in sensor responses over three cycles of measurements at each tested concentration. The MIP-QCM showed lower detection limits than conventional HPLC-UV, and faster response time compared to HPLC-UV and liquid chromatography-mass spectrometry (LC-MS).

Chemical structures of the antimalarial drugs: artemisinin, artemether (a methyl ether derivative of artemisinin), and lumefantrine.     

Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations

Zika virus (ZIKV) is one of the mosquito borne flavivirus with several outbreaks in past few years in tropical and subtropical regions. The non-structural proteins of flaviviruses are suitable active targets for inhibitory drugs due to their role in pathogenicity. In ZIKV, the non-structural protein 5 (NS5) RNA-Dependent RNA polymerase replicates its genome. Here we have performed virtual screening to identify suitable ligands that can potentially halt the ZIKV NS5 RNA dependent RNA polymerase (RdRp). During this process, we searched and screened a library of ligands against ZIKV NS5 RdRp. The selected ligands with significant binding energy and ligand-receptor interactions were further processed. Among the selected docked conformations, top five was further optimized at atomic level using molecular dynamic simulations followed by binding free energy calculations. The interactions of ligands with the target structure of ZIKV RdRp revealed that they form strong bonds within the active sites of the receptor molecule. The efficacy of these drugs against ZIKV can be further analyzed through in-vitro and in-vivo studies.     

A new finite element approach for near real‐time simulation of light propagation in locally advanced head and neck tumors

Background and Objectives

Several clinical studies suggest that interstitial photodynamic therapy (I‐PDT) may benefit patients with locally advanced head and neck cancer (LAHNC). For I‐PDT, the therapeutic light is delivered through optical fibers inserted into the target tumor. The complex anatomy of the head and neck requires careful planning of fiber insertions. Often the fibers' location and tumor optical properties may vary from the original plan therefore pretreatment planning needs near real‐time updating to account for any changes. The purpose of this work was to develop a finite element analysis (FEA) approach for near real‐time simulation of light propagation in LAHNC.

Methods

Our previously developed FEA for modeling light propagation in skin tissue was modified to simulate light propagation from interstitial optical fibers. The modified model was validated by comparing the calculations with measurements in a phantom mimicking tumor optical properties. We investigated the impact of mesh element size and growth rate on the computation time, and defined optimal settings for the FEA. We demonstrated how the optimized FEA can be used for simulating light propagation in two cases of LAHNC amenable to I‐PDT, as proof‐of‐concept.

Results

The modified FEA was in agreement with the measurements (P = 0.0271). The optimal maximum mesh size and growth rate were 0.005–0.02 m and 2–2.5 m/m, respectively. Using these settings the computation time for simulating light propagation in LAHNC was reduced from 25.9 to 3.7 minutes in one case, and 10.1 to 4 minutes in another case. There were minor differences (1.62%, 1.13%) between the radiant exposures calculated with either mesh in both cases.

Conclusions

Our FEA approach can be used to model light propagation from diffused optical fibers in complex heterogeneous geometries representing LAHNC. There is a range of maximum element size (MES) and maximum element growth rate (MEGR) that can be used to minimize the computation time of the FEA to 4 minutes. Lasers Surg. Med. 47:60–67, 2015. © 2015 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.     

The Ilizarov method for the treatment of complex tibial fractures and non-unions in a mass casualty setting: the 2005 earthquake in Pakistan

We report our experience in treating victims of the recent earthquake disaster in Pakistan. Our experience was based on two humanitarian missions to Islamabad: one in October 2005, 10 days after the earthquake, and the second in January 2006. The mission consisted of a team of orthopaedic surgeons and a second team of plastic surgeons. The orthopaedic team bought all the equipment for application of Ilizarov external fixators. We treated patients who had already received basic treatment in the region of the disaster and subsequently had been evacuated to Islamabad. During the first visit, we treated 12 injured limbs in 11 patients. Four of these patients were children. All cases consisted of complex multifragmentary fractures associated with severe crush injuries. All fractures involved the tibia, which were treated with Ilizarov external fixators. Nine fractures were type 3b open injuries. Eight were infected requiring debridement of infected bone and acute shortening. During a second visit, we reviewed all patients treated during our first mission. In addition, we treated 13 new patients with complex non-unions. Eight of these patients were deemed to be infected. All patients had previous treatment with monolateral fixators as well as soft tissue coverage procedures, except one patient who had had an IEF applied by another team. All these patients had revision surgery with circular frames. All patients from both groups were allowed to fully weight-bear post-operatively, after a short period of elevation to allow the flaps to take. Overall, all fractures united except one case who eventually had an amputation. Four patients had a corticotomy and lengthening, and three of them had a successful restoration of limb length. The fourth patient was the one with the eventual amputation.