Nanobiotic formulations as promising advances for combating MRSA resistance: susceptibilities and post-antibiotic effects of clindamycin,doxycycline, and linezolid

Antimicrobial activity and post-antibiotic effects (PAEs) are both important parameters in determination of the dosage regimen of antimicrobial agents. In the present study, antimicrobial activity and PAEs of clindamycin, doxycycline, linezolid, and their nanobiotic formulations were evaluated against two methicillin resistant Staphylococcus aureus clinical isolates (MRSA) encoded (MRSA-S1 and MRSA-S2). Nanobiotic formulations increased the susceptibility of MRSA isolates by 4–64 folds as compared to their conventional ones. The PAE values were determined after exposure of MRSA isolates for 1 h to 10× the MICs of the tested antibiotics. The duration of PAEs were recorded after bacterial growth in Mueller Hinton broth (MHB) free from antibiotic has been restored. The PAE values for MRSA-S1 were 2.5 h for the conventional antibiotics. However, the PAEs for nanobiotics were 4 h for both clindamycin and linezolid, while 3 h for doxycycline. For MRSA-S2, linezolid and linezolid nanobiotics PAEs were 3 h. PAEs of clindamycin and clindamycin nanobiotics were 3.75 h and 4 h, respectively. Doxycycline and doxycycline nanobiotics revealed the same PAEs patterns of 3.5 h. The findings of the current study may positively influence the pharmacodynamics of the antibiotics and consequently the dosage regimen of nanobiotics as well as on their clinical outcome.

Novel nanobiotic formulations of clindamycin, doxycycline, and linezolid were evaluated for the post-antibiotic effects against biofilm forming methicillin resistant Staphylococcus aureus (MRSA).     

To chelate or not to chelate in MDS: That is the question!

Myelodysplastic syndromes (MDS) are a heterogeneous group of hemopathies that exhibit physical manifestations with clinical consequences of bone marrow failure and inherent risk of progression to acute myeloid leukemia. Iron overload (IO) is common in MDS due to chronic transfusion support and disease-related alterations in iron metabolism. IO has been conclusively associated with inferior outcomes among MDS patients. Despite lack of randomized trials showing a survival impact of iron chelation therapy (ICT), ICT is recommended by experts and guidelines for select MDS patients with IO and is often used. The availability of effective oral ICT agents has reignited the controversy regarding ICT use in patients with MDS and IO. Here we summarize the studies evaluating the value of ICT in MDS and suggest a practical approach for use of these therapies. We also highlight controversies regarding use of ICT in MDS and discuss some ongoing efforts to answer these questions.     

Heterogeneous effects of obesity on mental health: Evidence from Mexico

Obesity can spread more easily if it is not perceived negatively. This issue may be more pronounced among the poor, a conjecture that we test in this paper. We start with general evidence on the concave relationship between income and obesity, both across countries and within Mexico, a country characterized by very unequal development levels and the highest obesity rate in the world. We suggest a general model that explains this stylized fact from a simple necessary condition, namely, the complementarity between nonfood consumption and health concerns. Then, we test the direct effect of overweight on mental health among Mexican women. We find a positive effect of obesity in the low consumption group and a depressing effect among the rich. This result is robust to the inclusion of a range of confounders (childhood conditions, lifestyle variables, food expenditure, and household shocks) and after instrumenting individual fatness by the variation in genetic predisposition. The complementarity between living standards and weight concerns may reflect different norms, different labor market penalties, or simply different returns to healthy time across the social spectrum.     

Risk factors of Egyptian male osteoporosis

Background: Osteoporosis (OP) is a growing health problem not only in women but also in men. Subjects and methods: This study was carried out on 100 healthy men, age range 30–65 years (mean ± SD, 44.65 ± 8.3). All were randomly recruited from Assiut city during the period January 2005 to January 2006. Complete clinical history included occupational history, smoking habit, physical activity and calcium intake. Complete clinical examination and anthropometric measurments were done. Laboratory investigations for serum calcium, phosphorus and osteocalcin were performed. Bone mineral density (BMD) was measured by calcaneal ultrasound. Results: Sixty‐three percent of participants had normal BMD, 37% had low BMD, (26% had quantitative bone ultrasound [QUS] T‐score –1 to –2.5 and 11% had QUS T‐score ≤ –2.5). Smoking and low physical activity were risk factors for low BMD. Significant positive correlations were found between BMD and body mass index, serum calcium, and osteocalcin and negative correlation with phosphorus. We concluded that low BMD occurs with high frequency in Egyptian men. Smoking, physical inactivity and low body index are significant risk factors. Low serum calcium, low serum osteocalcin and high serum phosphorus are biochemical risk factors of low BMD in males.     

Epidemiology of uncontrolled epilepsy in the Al-Kharga District,New Valley,Egypt

BackgroundDespite advances in treating epilepsy, uncontrolled epilepsy continues to be a major clinical problem. Therefore, this work aimed to study the epidemiology of uncontrolled epilepsy in Al-Kharga District, New Valley.MethodsThis study was carried out in 3 stages via door-to-door screening of the total population (62,583 persons). All suspected cases of epilepsy were subjected to case ascertainment, conventional ElectroEncephaloGraphy (EEG), and the Stanford-Binet Intelligence Scale. Patients who had been receiving suitable anti-epileptic drugs (AEDs) over the previous 6 months and were having active seizures were considered uncontrolled, according to Ohtsuka et al.²³ The patients underwent serum AED level estimation, video EEG monitoring, and brain MRIs. Fifty age- and gender-matched patients with controlled epilepsy were chosen for statistical analysis and compared with true intractable patients.ResultsA total of 437 patients with epilepsy were identified, 30.7% of whom (n = 134/437) were uncontrolled, with a prevalence of 2.1/1000. A total of 52.2% of uncontrolled patients (n = 70/134) were inappropriately treated, while 47.8% (n = 64/134) were compliant with appropriate treatments. Video monitoring EEG of compliant uncontrolled patients demonstrated that 78.1% patients (n = 50/64) had definite epilepsy, while 21.9% (n = 14/64) had psychogenic non-epileptic seizures (PNES). A logistic regression analysis revealed that status epilepticus, focal seizures, and mixed seizure types were risk factors for intractability.     

Regional expression and ultrastructural localization of EphA7 in the hippocampus and cerebellum of adult rat

EphA7 is expressed in the adult central nervous system (CNS), where its roles are yet poorly defined. We mapped its distribution using in situ hybridization (ISH) and immunohistochemistry (IHC) combined with light (LM) and electron microscopy (EM) in adult rat and mouse brain. The strongest ISH signal was in the hippocampal pyramidal and granule cell layers. Moderate levels were detected in habenula, striatum, amygdala, the cingulate, piriform and entorhinal cortex, and in cerebellum, notably the Purkinje cell layer. The IHC signal distribution was consistent with ISH results, with transport of the protein to processes, as exemplified in the hippocampal neuropil layers and weakly stained pyramidal cell layers. In contrast, in the cerebellum, the Purkinje cell bodies were the most strongly immunolabeled elements. EM localized the cell surface‐expression of EphA7 essentially in postsynaptic densities (PSDs) of dendritic spines and shafts, and on some astrocytic leaflets, in both hippocampus and cerebellum. Perikaryal and dendritic labeling was mostly intracellular, associated with the synthetic and trafficking machineries. Immunopositive vesicles were also observed in axons and axon terminals. Quantitative analysis in EM showed significant differences in the frequency of labeled elements between regions. Notably, labeled dendrites were ～3–5 times less frequent in cerebellum than in hippocampus, but they were individually endowed with ～10–40 times higher frequencies of PSDs, on their shafts and spines. The cell surface localization of EphA7, being preferentially in PSDs, and in perisynaptic astrocytic leaflets, provides morphologic evidence that EphA7 plays key roles in adult CNS synaptic maintenance, plasticity, or function. J. Comp. Neurol. 524:2462–2478, 2016. © 2016 Wiley Periodicals, Inc.