Development and Characterization of Biocompatible Mannose Functionalized Mesospheres: an Effective Chemotherapeutic Approach for Lung Cancer Targeting.

The aim of the present study was to analyze the lung targeting potential of surface engineered mesospheres loaded with doxorubicin hydrochloride (DOX). Gelatin-based DOX encapsulated mesospheres were prepared using a steric stabilization process and surface modified with mannose, using the amino group present on the surface of the mesospheres. Gelatin-DOX-mesospheres (M1) and gelatin-mannosylated-DOX-mesospheres (M2) were characterized for particle size, polydispersity index, zeta potential, and % entrapment efficiency which were found respectively 8.7 ± 0.35, 0.671 ± 0.018, 1.74 ± 0.27, and 80.4 ± 1.2 for (M1) and 9.8 ± 0.41, 0.625 ± 0.010, 0.85 ± 0.11, and 75.1 ± 0.7 for (M2). Furthermore, the mesospheres were characterized by FTIR, DSC, SEM, and TEM. In vitro drug release study of optimized formulation was carried out using the dialysis tube method. The cumulative percent drug release was found to be 79.2 ± 0.1% and 69.6 ± 0.52% respectively for gelatin-DOX-mesospheres and gelatin-mannosylated-DOX-mesospheres. In vitro cytotoxicity of formulations was determined using xenograft A-549 tumor cell lines. The cytotoxicity recorded as IC50 was more in the case of M2 compared to M1. In addition, mesospheres exhibited minimal hemolytic toxicity and appear to be promising for sustained drug delivery of DOX to the lungs. Cytotoxicity assay was conducted on the A-549 cell line. The results revealed that gelatin-mannosylated-DOX-mesospheres were maximally cytotoxic as compared to free DOX as well as gelatin-DOX-mesospheres. The lung's accumulation of drug was measured and found maximum after administration of M2. It may, therefore, be inferred that gelatin-mannosylated-DOX-mesospheres are capable to carry bioactive(s) and can be used specifically to target the lung cancer with minimal side effects.

Papilloedema: diffusion-weighted imaging of optic nerve head.

AIM: To establish the correlation between clinical grading of papilloedema and diffusion abnormalities of optic nerve head (ONH) on diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Brain magnetic resonance imaging (MRI), including readout segmented echo planar imaging-based DWI, was performed in 32 patients with papilloedema and the same number of age- and sex-matched controls. Clinical grading of papilloedema was done according to the modified Frisén scale. Two neuroradiologists independently evaluated the MRI for ONH hyperintensity and apparent diffusion coefficient (ADC) value of ONH. The comparison between papilloedema clinical grade and qualitative grade of ONH hyperintensity and its presence between cases and control groups were done using the Chi-square test and Fisher's exact test, respectively. The comparison between mean ADC value of ONH among different grades and between cases and controls were done using analysis of variance (ANOVA)-F-test and Student's t-test, respectively. Receiver operating characteristic (ROC) analysis was done to calculate a cut-off ADC value between the case and control groups. RESULTS: Significant correlation between ONH hyperintensity and mean ADC value of ONH with clinical grades of papilloedema and between cases and control groups were found. ONH hyperintensity was found to be a highly sensitive (87.5% for both) and specific (specificity 97.1% and 98.6% for two observers) sign of papilloedema. A mean cut-off ONH ADC value was found to have high sensitivity (96.83%) and specificity (95.31%) to distinguish between the cases and controls. CONCLUSIONS: Diffusion parameters of ONH have significant correlation with clinical grading of papilloedema and can serve as a surrogate marker for intracranial pressure.

Mannose functionalized plain and endosomolytic nanocomposite(s)-based approach for the induction of effective antitumor immune response in C57BL/6 mice melanoma model.

The goal of present study to assess the antigen specific immunopotentiation effect of mannose functionalized endosomolytic and conventional nanocomposite(s) based combination approach using C57BL/6 mice melanoma model. Endosomolytic and conventional nanocomposite(s) were prepared by double emulsification method. The optimized formulation was extensively characterized for average particle size, zeta potential and PDI of nanocomposite(s) which were measured in range of ≈200 nm, 0.111 ± 0.024, -23.4 ± 2.0 mV, respectively. pH-dependent morphological changes in the surface of MRPRPNs and PRPNs were analyzed by using surface electron microscopy at different time intervals. The cellular uptake assessment of developed formulations were followed by using RAW 264.7 macrophage cell lines. Results revealed that after immunizing B16F10 melanoma cells implanted C57BL/6 mice with combination [endosomolytic and conventional nanocomposite(s)] of nanocomposite(s), a significant increase in the interleukins level i.e. IL-2, IFN-ϒ, IL-12 and IL-6 and OVA Ag(s) specific antibody responses were recorded. Consequently, a strong immunological response was elicited with specific polarization contributing to humoral and activation of CD8+ to cellular responses. Finding of histological examination also support the potential of therapeutic outcome. The present approach based on mannose surface functionalization for targeting to antigen presenting cells and pH-dependent prompt endosomal release and escape can be a promising system for efficient cancer immunotherapy.

A review of the potential of medicinal plants in the management and treatment of male sexual dysfunction.

Male sexual dysfunction is a common disorder that appears to be a consequence of a wide range of physical and psychological conditions. Due to mental stress, insufficient physical exercise and various aetiological factors, human being's life is becoming less pleasant, which leads to incapability to have sexual pleasure. The allopathic drugs used for sexual dysfunction are believed to produce a variety of side effects and affect other physiological processes and, ultimately, general health. Therefore, the search for natural supplement from medicinal plants is being intensified probably because of less side effects availability and affordability. Ethnobotanical surveys have indicated a large number of plants traditionally used as aphrodisiacs but only few of them are scientifically validated for the management and treatment of male sexual dysfunction. This article has summarised the medicinal plants traditionally recommended and scientifically validated for the management and treatment of male sexual dysfunction.

Towards personalizing haemophilia care: using the Haemophilia Severity Score to assess 178 patients in a single institution.

The phenotypic variability in haemophilia is well documented; however, the biological basis beyond factor VIII and IX activities to explain the differing clinical pictures of the disease remains unclear. It has therefore been of interest to explore other modulators of the disease's variability. Furthermore, a scoring system that reflects the multiple facets of haemophilia symptoms would be useful to compare patients via a comprehensive assessment tool. To this end, Schulman et al., created a measure known as the Haemophilia Severity Score (HSS) as one way to compare phenotypic severity. The aim of this study was to document the differing symptomatology of haemophilia patients using the HSS. Clinical data for 178 haemophilia patients without inhibitors were reviewed and annual incidence of haemarthrosis, orthopaedic joint scores and annual factor usage calculated. Each parameter was then entered into the formula to create the HSS for haemophilia A and B patients with mild, moderate and severe factor deficiencies. Variability in the HSS for patients with the same baseline level of factor was observed for all three deficiency levels and both haemophilia types. In addition, we found that moderate and severe haemophilic B patients tended to have more morbidity based on the above calculations than the haemophilic A counterparts. The HSS is a comprehensive tool that allows for easy numerical comparison of haemophilic patients and elucidates the variable clinical presentation of the disease. The HSS could be used to stratify patients via other possible modulators of haemophilia and discover other aetiologies of the disease.

Improved outcomes in the management of high-risk incisional hernias utilizing biological mesh and soft-tissue reconstruction: a single center experience.

INTRODUCTION: Repair of incisional hernias is complex in the setting of previous/current infection, loss of domain and bowel involvement, and is often on the background of significant co-morbidities. Reported repair techniques are associated with significant morbidity and led our unit to develop a novel technique for complex incisional hernia repair. METHODS: A retrospective case notes review of all high-risk (Ventral Hernia Working Group grade 2-4) incisional hernia repairs was undertaken. Standardized repair involved resection of attenuated soft tissue and hernia sac (bioburden reduction), component separation (where necessary), intra-peritoneal Strattice™ biological mesh insertion, midline fascial closure, and soft-tissue reconstruction, performed in combination with a plastic surgeon as a single-stage procedure. RESULTS: A total of 58 patients underwent hernia repair between February 2009 and September 2012 (median age 59 years; 59 % female). Eleven patients (19 %) were grade 4, 19 (33 %) were grade 3, and 28 (48 %) were grade 2. Nineteen (33 %) were recurrent hernias, and midline fascial closure was achieved in 52 (90 %). Early complications included 15 (26 %) surgical-site occurrences, three (5 %) respiratory complications, two (3 %) cardiac complications, and two (3 %) urinary tract infections. Follow-up has revealed three (5 %) asymptomatic hernia recurrences and no patients requiring mesh explantation. CONCLUSIONS: This technique was associated with a low risk of surgical site occurrences and hernia recurrence, with no requirements for mesh explantation. Repair of such complex incisional hernias remains challenging, and further randomized controlled trials are required to elucidate the optimal method of closure and mesh type.

Prolonged laparoscopic surgery is associated with an increased risk of vertebral disc prolapse.

The benefits of laparoscopic surgery to the patient are well recognised, however it is more physically demanding on the surgeon. A survey was sent to members of the British Society of Gynaecological Endoscopy to ascertain musculoskeletal symptoms and vertebral disc prolapse thought to occur as a result of undertaking laparoscopic surgery. A total of 19 (15%) participants were diagnosed with a vertebral disc prolapse, for which one-third needed definitive treatment. There was a statistically significant association with length of practice and numbers of hours worked per week, with the risk of disc prolapse. There was a multitude of other musculoskeletal symptoms reported. These findings suggest that gynaecological laparoscopic surgery carries a high personal health risk to the surgeon, which is likely to increase as the capability and superiority of laparoscopic techniques develop. There is an urgent need to explore further the ergonomic impact of laparoscopic work to enable improvements to be made.

Study on validity of a rapid diagnostic test kit versus light microscopy for malaria diagnosis in Ahmedabad city, India.

Light microscopy of blood smears for diagnosis of malaria in the field has several limitations, notably delays in diagnosis. This study in Ahmedabad in Gujarat State, India, evaluated the diagnostic performance of a rapid diagnostic test for malaria (SD Bioline Malaria Ag P.f/Pan) versus blood smear examination as the gold standard. All fever cases presenting at 13 urban health centres were subjected to rapid diagnostic testing and thick and thin blood smears. A total of 677 cases with fever were examined; 135 (20.0%) tested positive by rapid diagnostic test and 86 (12.7%) by blood smear. The sensitivity of the rapid diagnostic test for malaria was 98.8%, specificity was 91.5%, positive predictive value 63.0% and negative predictive value 99.8%. For detection of Plasmodium falciparum the sensitivity of rapid diagnostic test was 100% and specificity was 97.3%. The results show the acceptability of the rapid test as an alternative to light microscopy in the field setting.

Clinicopathological association of mucormycosis in COVID 19 pandemic.

Context: Coinfection and superadded infections in patients with coronavirus disease 2019 (COVID-19) has been reported on multiple series. The emerging second wave of the pandemic has come with a lot of changes, especially in developing countries like India. One of such changes is sudden, significant rise in mucormycosis cases. Aims: To find out clinicopathological association of invasive mucormycosis with COVID-19 infection status and immunocompromised state. Settings and Design: A cross-sectional study done at a tertiary care centre. Methods and Material: All cases admitted in the dedicated mucormycosis ward between 1-06-2021 and 15-06-2021 were included in the study. The cases were admitted with suspicion of mucormycosis. The histopathological results were correlated with KOH mount and radiological reports. The clinicopathological association of occurrence of mucormycosis in post-covid and non-COVID patients along with other risk factors. Statistical Analysis Used: Odds ratio, chi square test were used to find the association using MS Excel 2010 and SPSS. Results: Thirty-six (81.82%) cases were of the post-COVID status, and 8 cases were non-COVID status. Out of 36 post-COVID patients, 33 (91.67%) showed evidence of invasive mucormycosis and of 8 non-COVIDpatients, 7 had evidence of mucormycosis (odds ratio = 1.57). Out of the total diagnosed cases of mucormycosis, 21 (52.5%) patients were known cases of diabetes mellitus (DM), and 7 (17.5%) cases of newly diagnosed hyperglycemia. Thirty (75%) patients out of 40 had some form of immunocompromised state. This shows statistically significant association of DM and immunocompromised state with the occurrence of mucormycosis in post-COVID patients (chi square value2 = 6.891, P value = 0.008). Twenty-five patients had the history of steroid use during the treatment of COVID-19. Conclusions: The infection with COVID-19 definitely increases the odds of contracting mucormycosis, but most of the cases had diabetes mellitus. So, it is possible that COVID-19 virus predisposes individuals to invasive fungal infection by precipitating DM.

Validity and reliability of haemoglobin colour scale and its comparison with clinical signs in diagnosing anaemia in pregnancy in Ahmedabad, India.

This study compared the validity of the haemoglobin colour scale (HCS) and clinical signs in diagnosing anaemia against Sahli's haemoglobinometer method as the gold standard, and assessed the reliability of HCS. The sample comprised 129 pregnant women recruited from 6 urban health centres in Ahmedabad. The prevalence of anaemia was 69.8% by Sahli's method, 78.3% by HCS and 89.9% by clinical signs; there was no statistically significant difference between Sahli's method and HCS whereas there was between Sahlis method and clinical signs. The mean haemoglobin level by Sahli's method and HCS differed significantly. The sensitivity, specificity, positive predictive value and negative predictive value of HCS was 83.3%, 33.3%, 74.3% and 46.4% respectively and that of clinical signs was 91.1%, 12.8%, 70.7% and 38.5% respectively. Interobserver agreement for HCS was moderate (K = 0.43). Clinical signs are better than HCS for diagnosing anaemia. HCS can be used in the field provided assessors are adequately trained.

Multicompartment systems: A putative carrier for combined drug delivery and targeting.

In this review, we discuss recent developments in multicompartment systems commonly referred to as vesosomes, as well as their method of preparation, surface modifications, and clinical potential. Vesosomal systems are able to entrap more than one drug moiety and can be customized for site-specific delivery. We focus in particular on the possible reticuloendothelial system (RES) - mediated accumulation of vesosomes, and their application in tumor targeting, as areas for further investigation.

Determination of potential drug-drug interactions in prescription orders dispensed in a community pharmacy setting using Micromedex® and Lexicomp®: a retrospective observational study.

Background Community pharmacists have a role in identifying drug-drug interactions (DDIs) when processing prescription orders and dispensing medications to patients. The harmful effects of DDIs can be prevented or minimized by using an electronic DDI checker to screen for potential DDIs (pDDIs). However, different DDI checkers have variable rates of detecting pDDIs. Aim To estimate the prevalence of pDDIs in prescriptions dispensed in a community pharmacy setting using two electronic DDI databases and to evaluate the association between the pDDIs and contributory factors. Method Eligible prescription orders dispensed by a community pharmacy chain in Qatar from January to July 2020 were included in this retrospective observational study. For each prescription, Micromedex® and Lexicomp® were simultaneously used to identify pDDIs, and the interactions categorized based on severity and risk rating. Results Seven hundred-twenty prescriptions met the inclusion criteria, of which Micromedex® and Lexicomp® respectively identified 125 prescriptions (17.4%) and 230 prescriptions (31.9%) as having at least one pDDI. Moderate strength of agreement was found between Lexicomp® and Micromedex® in identifying pDDIs (Cohen's Kappa = 0.546). Micromedex® classified 61.6% of DDIs as major severity, while Lexicomp® classified 30.8% as major severity. The number of concurrent medications per prescription was significantly and positively associated with pDDI. Conclusion This study demonstrates a high prevalence of pDDIs among prescriptions dispensed in a community pharmacy setting. It is advisable that community pharmacists in Qatar, who typically do not have access to computerized patient profiles, use these DDI checkers to ensure all pDDIs are communicated to respective prescribers for appropriate action.

Systematic review and meta-analysis of laparoscopic Nissen fundoplication with or without division of the short gastric vessels.

BACKGROUND: The aim of this meta-analysis was to provide a pooled analysis of individual trials comparing clinical outcome following laparoscopic Nissen fundoplication with or without division of the short gastric vessels (SGVs). METHODS: Primary outcome measures were the requirement for reoperation, and the presence of postoperative gastro-oesophageal reflux and postoperative dysphagia. Secondary outcome measures were duration of operation, length of hospital stay, postoperative complications (within 30 days of surgery), postoperative gas bloat syndrome, lower oesophageal sphincter resting pressure and DeMeester score. Pooled odds ratios were calculated for categorical outcomes, and weighted mean differences for secondary continuous outcomes, using random-effects models for meta-analysis. RESULTS: Five randomized trials were included in the analysis. There was no statistically significant effect on the requirement for reoperation, or presence of postoperative dysphagia or reflux. SGV division was associated with a longer duration of operation and a reduced postoperative lower oesophageal sphincter pressure. There was no statistically significant difference in length of hospital stay, postoperative complications, postoperative gas bloat syndrome or DeMeester score. CONCLUSION: This meta-analysis has demonstrated that clinical outcome following laparoscopic Nissen fundoplication appears to be similar regardless of whether the short gastric vessels are divided. However, it is not possible to exclude many potentially important clinical differences and further studies are needed.

The management of women with thoracic endometriosis: a national survey of British gynaecological endoscopists.

OBJECTIVES: This study evaluates current national opinions on screening, diagnosis, and management of thoracic endometriosis. BACKGROUND: Thoracic endometriosis is a rare but serious condition with four main clinical presentations: pneumothorax, haemoptysis, haemothorax, and pulmonary nodules. There are no specialist centres in the United Kingdom despite growing patient desire for recognition, investigation, and treatment. METHODS: We distributed a multiple-choice email survey to senior members of the British Society for Gynaecological Endoscopy. Descriptive statistics were used to present the results. Results: We received 67 responses from experienced clinicians having provided over 800 combined years of endometriosis patient care. The majority of respondents managed over 100 endometriosis patients annually, for more than five years. Over one third had never managed a patient with symptomatic thoracic endometriosis; just 9% had managed more than 30 cases over the course of their career. Screening varied by modality with only 4% of clinicians always taking a history of respiratory symptoms while 69% would always screen for diaphragmatic endometriosis during laparoscopy. The management of symptomatic thoracic endometriosis varied widely with the commonest treatment being surgery followed by hormonal therapies. Regarding management, 71% of respondents felt the team should comprise of four or more different specialists, and 56% believed care should be centralised either regionally or nationally. CONCLUSIONS: Thoracic endometriosis is poorly screened for amongst clinicians with varied management lacking a common diagnostic or therapeutic pathway in the United Kingdom. Specialists expressed a preference for women to be managed in a large multidisciplinary team setting at a regional or national level.

Cognitive Performance and Neuro-Metabolites in HIV Using 3T Magnetic Resonance Spectroscopy: A Cross-Sectional Study from India.

BACKGROUND: Cognitive impairment in patients with human immunodeficiency virus (HIV) is associated with higher morbidity. The prevalence of the metabolite changes in the brain associated with cognitive impairment in anti-retroviral therapy naïve patients with HIV is unknown. OBJECTIVE: To estimate the prevalence of the neurometabolites associated with cognitive impairment in antiretroviral therapy (ART) naïve patients with HIV. METHODS: We conducted a cross-sectional study among ART naïve patients with HIV aged 18-50 years in a tertiary care center in India. Cognition was tested using the Post Graduate Institute battery of brain dysfunction across five domains; memory, attention-information processing, abstraction executive, complex perceptual, and simple motor skills. We assessed the total N-acetyl aspartyl (tNAA), creatine (tCr) and glutamate + glutamine (Glx) using 3T magnetic resonance spectroscopy. Cognitive impairment was defined as an impairment in ≥2 domains. RESULTS: Among 43 patients eligible for this study, the median age was 32 years (IQR 29, 40) and 30% were women. Median CD4 count and viral load were 317 cells/µL (IQR 157, 456) and 9.3 copies/ µL (IQR 1.4, 38), respectively. Impairment in at least one cognitive domain was present in 32 patients (74.4%). Impairment in simple motor skills and memory was present in 46.5% and 44% of patients, respectively. Cognitive impairment, defined by impairment in ≥2 domains, was found in 22 (51.2%) patients. There was a trend towards higher concentration of tNAA (7.3 vs. 7.0 mmol/kg), tGlx (9.1 vs. 8.2 mmol/kg), and tCr (5.5 vs. 5.2 mmol/kg) in the frontal lobe of patients with cognitive impairment vs. without cognitive impairment but it did not reach statistical significance (p>0.05 for all). There was no difference in the concentration of these metabolites in the two groups in the basal ganglia. CONCLUSION: There is a high prevalence of cognitive impairment in ART naïve patients with HIV. There is no difference in metabolites in patients with or without cognitive impairment. Further studies, with longitudinal follow-up are required to understand the underlying pathophysiological mechanisms.

Evidence of community pharmacists' response preparedness during COVID-19 public health crisis: A cross-sectional study.

INTRODUCTION: Community pharmacists are often the first point of contact for the public, especially during pandemics. As outlined by the International Pharmaceutical Federation, community pharmacists have an important public health role during this Coronavirus Disease 2019 (COVID-19) public health emergency. We therefore investigated the current practices, response preparedness and professional development needs of community pharmacists in Qatar. METHODOLOGY: A descriptive cross-sectional online 38-item questionnaire-based survey constructed on evidence-based public health roles of pharmacists was conducted between 28 May and 18 June 2020. Questions related to current practices required responses on a 5-point Likert-type scale ranging from "always" to "never". The questionnaire was evaluated for validity and the reliability analysis showed a Cronbach's alpha coefficient of 0.921. RESULTS: The response (n = 311) rate for the survey was 34.2%. More than 75% of pharmacists "always" encouraged and practiced hygiene and social distancing measures. On the other hand, the proportion of pharmacists "always" involved in patient assessment, education or providing information related to COVID-19 and application of evidence-based protocol ranged from 32 to 73%. The vast majority (87-96%) of pharmacists indicated that they needed professional development related to COVID-19. Overall, 77% of pharmacists either "strongly agreed" or "agreed" that they have all the necessary COVID-19 related emergency response preparedness and training. Country from which pharmacists obtained their first degree, and the type of pharmacy where they practice influenced their overall perception toward emergency response preparedness. CONCLUSIONS: Community pharmacists in Qatar are willing to receive additional training related to COVID-19 public health crisis despite being prepared to engage with patients.

Synthesis and Solid State Structure of Fluorous Probe Molecules for Fluorous Separation Applications.

A series of colored hydrocarbon and fluorocarbon tagged 1-fluoro-4-alkylamino-anthraquinones and 1,4-bis-alkylamino-anthraquinone probe molecules were synthesized from a (fluorinated) alkyl amine and 1,4-difluoroanthraquinone to aid in the development of fluorous separation applications. The anthraquinones displayed stacking of the anthraquinone tricycle and interdigitation of the (fluorinated) alkyl chains in the solid state. Furthermore, intramolecular N-H···O hydrogen bonds forced the hydrocarbon and fluorocarbon tags into a conformation pointing away from the anthraquinone tricycle, with the angle of the tricycle plane normal and the main (fluorinated) alkyl vector ranging from 1 to 39°. Separation of the probe molecules on fluorous silica gel showed that the degree of fluorination of the probe molecules plays only a minor role with most eluents (e.g., hexane-ethyl acetate and methyl nonafluorobutyl ethers-ethyl acetate). However, toluene as eluent caused a pronounced separation by degree of fluorination for fluorocarbon, but not hydrocarbon tagged probe molecules on both silica gel and fluorous silica gel. These studies suggest that hydrocarbon and fluorocarbon tagged anthraquinones are useful probe molecules for the development of laboratory scale fluorous separation applications.

Nanobiotechnological modules as molecular target tracker for the treatment and prevention of malaria: options and opportunity.

Malaria is one of the major infectious diseases that remains a constant challenge to human being mainly due to the emergence of drug-resistant strains of parasite and also the availability of drugs, which are non-specific for their pharmacodynamic activity and known to be associated with multiple side effects. The disease has acquired endemic proportions in tropical countries where the hygienic conditions are not satisfactory while the environmental conditions favor the proliferation of parasite and its transmission, particularly through the female anopheles. It is obvious that to square up the problems, there is a need for designing and development of more effective drugs, which can combat the drug-resistant strains of the parasite. Molecular biology of the parasite and its homing into host cellular tropics provide multiple drug targets that could judiciously be considered for engineering and designing of new generation antimalarial drugs and also drug delivery systems. Though the recent reports document that against malaria parasite the vaccine could be developed, nevertheless, due to smart mutational change overs by the parasite, it is able to bypass the immune surveillance. The developed vaccine therefore failed to assure absolute protection against the malarial infection. In the conventional mode of treatment antimalarial drugs, the dose and dosage regimen that is followed at large crops up the contraindicative manifestations, and hence compromising the effective treatment. The emerging trends and new updates in contemporary biological sciences, material sciences, and drug delivery domain have enabled us with the availability of a multitude of mode and modules which could plunge upon the nanotechnology in particular to treat this challenging infection. The nanotechnology-based option may be tuned or customized as per the requirements to mark and target i.e. the infected RBCs, for targeted drug delivery. Graphical abstract.

Identification of differentially expressed genes profiles in a combined mouse model of Parkinsonism and colitis.

Different cellular mechanisms have been described as being potentially involved in the progression of neurodegeneration in Parkinson's disease, although their role is still unclear. The present study aimed to identify in detail, through differentially expressed genes analysis by bioinformatics approaches, the molecular mechanisms triggered after a systemic insult in parkinsonian mice. To address this objective, we combined a dextran sodium sulfate (DSS)-induced ulcerative colitis experimental mice model with an acute 1-methyl-4-phenyl-1,2,3,6-tetradropyridine (MPTP) intoxication. The animals were divided into four experimental groups based on the different treatments: (i) control, (ii) DSS, (iii) MPTP and (iv) MPTP + DSS. The data obtained by microarray and functional enrichment analysis point out the implication of different molecular mechanisms depending on the experimental condition. We see, in the striatum of animals intoxicated only with DSS, dysfunction processes related to the blood. On the other hand, oxidative stress processes are more prominent at the MPTP intoxicated mice. Finally, differentially expressed genes within the MPTP + DSS show functional enrichment in inflammation and programmed cell death. Interestingly, we identify a significant synergistic negative effect of both toxins since the expression of differentially expressed genes (DEGs) related to balanced cellular homeostasis was not enough to prevent processes associated with cell death. This work provides detailed insights into the involvement of systemic inflammation, triggered after an insult in the colon, in the progression of the degeneration in Parkinsonism. In this way, we will be able to identify promising therapeutic targets that prevent the contribution of inflammatory processes in the progression of Parkinson's disease.

STI management in Tanzanian private drugstores: practices and roles of drug sellers.

OBJECTIVES: To describe the role and possible contribution of private drugstores in sexually transmitted infection (STI) management in rural Tanzania. METHODS: A cross-sectional study that included drug sellers in private drugstores in eight districts of Tanzania. Data collected through interviews with drug sellers and the simulated client method presenting a male and female STI case. "QATI" scores (Questions, Advice, Treatment and drug Information) were developed to describe overall STI management. RESULTS: Although 74% of drug sellers stated that there were no STI-related drugs in the store, medications were dispensed in 78% of male and 63% of female simulated client visits. The clients were dispensed drugs recommended in the Tanzanian guidelines for syndromic management of urethral or vaginal discharge in 80% of male and 90% of female cases. Drug sellers dispensed antibiotics during 76% of male and 35% of female simulated client visits. Dosage regimens were often incorrect and complete syndromic management rarely provided. Most drug sellers agreed that it is within their professional role to give information on STI treatment (89%) and prevention (95%). Drug-use information was almost always provided. Advice was however seldom given and questions occasionally asked. Overall STI management was better for men than for women. CONCLUSIONS: The drug sellers, although aware of the prescription-only status of antibiotics, saw themselves as having a role in STI management and were ready to provide drugs. In this resource-limited setting, drug sellers could provide effective and safe STI management especially to male patients if given appropriate tools to improve practice. The consequences of this for official policy need to be discussed.