The objective of this study was to evaluate the feasibility, safety, and potential benefits of laparoscopic gastrectomy (LG) comparing with open gastrectomy (OG) in elderly population.Studies comparing LG with OG for elderly population with gastric cancer, published between January 1994 and July 2015, were identified in the PubMed, Embase, and ISI Web of Science databases. Operative outcomes  and postoperative outcomes  were included and analyzed. The Newcastle-Ottawa Scale was used to assess the quality of the pooled study. A funnel plot was used to evaluate the publication bias.P < 0.01), earlier time to first ambulation , first flatus , and oral intake , postoperative hospital stay , lower overall postoperative complication rate (odd ratio (OR) 0.39; 95 % CI 0.28 to 0.55; P < 0.01), less surgical complications , medical complication , incisional complication , and pulmonary infection . No significant differences were observed between LG and OG for the number of harvested lymph nodes. However, LG had longer operative times .Seven studies totaling 845 patients were included in the meta-analysis. LG in comparison to OG showed less intraoperative blood loss (weighted mean difference (WMD) −127.47; 95 % confidence interval (CI) −202.79 to −52.16; LG is a feasible and safe approach for elderly patients with gastric cancer. Compared with OG, LG has less blood loss, faster postoperative recovery, and reduced postoperative morbidity. Gastric cancer remains one of the leading causes of cancer-related death worldwide, especially in East Asia –4. RadicDespite of controversy, laparoscopic gastrectomy (LG) has been developed as an innovation in the management of gastric cancer –8. Many Articles published from January 1994 to July 2015 were searched in the PubMed, Embase, and ISI Web of Science databases. The search strategy was performed using the following terms: “gastric cancer,” “gastric adenocarcinoma,” “gastric neoplasms,” “laparoscopy,” “laparoscopic,” “elderly,” “old,” and “aged.” All abstracts retrieved from the electronic databases were screened. Then, the full texts were retrieved when abstracts were relevant. The references of all relevant articles were also manually searched for potentially relevant studies.Eligibility criteria included the following: (1) histologically confirmed gastric cancer; (2) published studies comparing LG with OG for gastric cancer; (3) inclusion of elderly patients; and (4) availability of data on information of at least three outcome measures. Exclusion criteria included the following: (1) recurrent gastric cancer; (2) hand-assisted surgery or robotic surgery; (3) combined with other malignancies; (4) abstracts presented at meetings, review articles, case report, or letters; and (5) palliative gastrectomy. If more than one study of a single institution existed, the study with the most recent or the most informative data was included unless the relevant outcomes were only published in earlier version.Two reviewers independently extracted and checked data using a standard form. Disagreements in data extraction were resolved through discussion and consensus of the study team. The following data were extracted from each study: study name, study period, sample size, age, body mass index (BMI), comorbidity, extent of lymph node dissection, method of gastrectomy, tumor size, tumor location, operation time, intraoperative blood loss, number of harvested lymph nodes, time to first flatus, time to first oral intake, length of postoperative hospital stay, and postoperative complications. The qualities of studies were evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) . StudiesI2 [P > 0.05 or I2 < 50 %), the pooled effects were calculated using a fixed model [P < 0.05 was considered statistically significant.Dichotomous variables were evaluated by using odds ratio (OR) with a 95 % confidence interval (95 % CI), and continuous variables were analyzed using the weighted mean difference (WMD) with a 95 % CI. If the study provided medians and ranges instead of means and standard deviations (SDs), the means and SDs were calculated using the method described by Hozo et al. . HeterogI2 . If dataed model . Otherwied model . PublicaThe search strategy initially identified 2069 studies. After exclusion of irrelevant studies, 20 potentially relevant articles were obtained for assessment. Thirteen studies were excluded due to non-comparative studies, did not compare LG with OG, and including palliative gastrectomy cases. Finally, seven studies (three from Japan and four from China) published between 2004 and 2015 were included . The PRIP < 0.01; Fig. P < 0.01; Fig. P = 0.11; Fig. All seven pooled studies reported the operation time and intraoperative blood loss. Our meta-analysis suggested LG was associated with a reduction in intraoperative blood loss  and worse disease-specific mortality even if the tumor is resected curatively . One of In accordance with previous studies –35, the As a general benefit of laparoscopic techniques, the LG group was favored with less intraoperative blood loss. High heterogeneity between groups was observed in our study, which was likely to relate with the diversity of surgeons’ experience and methods to estimate the blood loss. This notable benefit mainly attributed to the nature of laparoscopic techniques. Magnified operation view facilitates meticulous manipulation. On the other hand, using harmonic instruments contribute to dissecting vessels around the stomach precisely and efficiently . Less blP > 0.05) [Because none of the pooled studies reported the hazard ratios and its 95 % CI and the Kaplan-Meier curves in several pooled studies were of poor quality, we did not analyze the pooled 5-year OS rate. However, all three pooled studies reported that a 5-year OS rate of LG was comparable with OG. Though indirectly, the number of retrieved lymph nodes is usually used as an indicator of the oncologic adequacy of gastrectomy. In our study, no significant difference of retrieved lymph nodes was observed between two groups. The number of retrieved lymph nodes in both the LG and OG group was more than 15 as recommended , which w > 0.05) . The aveOur studies also had some limitations, which should be taken into consideration before clinical practices. First, there was no randomized controlled study included in this study. Potential bias may exist in the selection of patients into the LG and OG group. Second, heterogeneity in studies with different cutoff age of elderly patients may also decrease the plausibility of the results. Third, the overall sample size of our study remained limited, and the inclusion of some small sample size studies or the method to estimate means and SDs described by Hozo may also result in bias. Fourth, this meta-analysis only included studies published in English or Chinese which may omit some important studies in other languages. Other biases may lie in that all pooled studies were from East Asia while no article comparing the LG and OG from other regions was retrieved. Nevertheless, Singh et al. reported that Western elderly patients could also undergo laparoscopic gastrectomy with low postoperative morbidity rate (3/20), suggesting the superior safety of LG in elderly patient .In conclusion, LG is a feasible and safe approach for elderly patients with gastric cancer. Compared with its open counterpart, LG has less blood loss, faster postoperative recovery, and reduced postoperative morbidity.


Aims. To synthesize, characterize, and analyze antimicrobial activity of AgNPs of Escherichia hermannii (SHE), Citrobacter sedlakii (S11P), and Pseudomonas putida (S5). Methods. The synthesized AgNPs were examined using ultraviolet-visible spectroscopy (UV-vis) and, zeta potential, and the size and the morphology obtained from the three different isolates were also confirmed by TEM. Results. Among the three isolates tested, SHE showed the best antimicrobial activity due to the presence of small (4–12 nm) and stable (−22 mV) AgNPs. Stability of AgNPs was also investigated and found to be dependent on the nature of isolates. Conclusion. Produced AgNPs showed particle stability and antimicrobial efficacy up to 90 days of production. Our AgNPs exhibited greater antimicrobial activity compared with gentamicin against P. aeruginosa isolates and vancomycin against S. aureus and MRSA isolates at very low concentration (0.0002 mg per Microliters). Staphylococcus aureus MRSA in some countries [Multidrug resistance is a growing problem all over the world. The widespread and uncontrolled use of antibiotics has led to resistance to conventional antimicrobial agents for many bacterial pathogens and poses a major health threat. For instance, more than 25% of insidious staphylococcal isolates are methicillin resistantountries . Silver ountries , and funMetal nanoparticles (NPs)  have been the subject of ample research interest in the last few years, due to their exciting size-dependent electrical, optical, physical, and chemical properties. In particular, colloidal silver nanoparticles (AgNPs) have attracted increasing research attention in the field of microbiology –8. Since Lactobacillus strains 500 nm [ Bacillus megaterium 46.9 nm [ Klebsiella pneumonia 50 nm [ Bacillus licheniformis 50 nm [ Corynebacterium sp. 10–15 nm [ Escherichia coli 1–100 nm [ Proteus mirabilis 10–20 nm [ Bacillus sp. 5–15 nm [ S. aureus 1–100 nm [ Pseudomonas aeruginosa 13 nm [In response, biological method of preparing metal nanoparticles  seems to be an interesting route for green chemistry. In this regard, several microorganisms including bacteria, yeasts, and fungi have been used –19. Manys 500 nm , Bacilluia 50 nm , Bacilluis 50 nm , Coryneb10–15 nm , Escheri1–100 nm , 24, Pro10–20 nm , Bacillu 5–15 nm , S. aure1–100 nm , and Psesa 13 nm .To the best of our knowledge, this is the first report to show the production of AgNPs using the supernatant of three new species collected from the Saudi environment. The synthesized nanoparticles were characterized by different methods such as UV-vis, zeta potential, and TEM. The colloidal AgNPs were also evaluated for antimicrobial activity against Gram-positive and Gram-negative pathogens. Escherichia hermannii (isolate SHE), Citrobacter sedlakii (isolate S11P), and Pseudomonas putida (isolate S5). Pseudomonas selective medium (cetrimide agar) was used in isolation and identification of Pseudomonas isolates. Ethylene Methylene Blue (EMB) medium was used to isolate and verify bacterial isolates belonging to Enterobacteriaceae.Bacterial isolates were extracted from soil samples, which were collected from different geographical areas in Riyadh, Kingdom of Saudi Arabia. Such areas have been known to be contaminated with traces of metal, that is, the old industrial area, the new industrial area, Khazzan area, and Al-Shimasi area. The bacteria were isolated by plating dilutions of soil samples in saline solution (0.9% NaCl) on nutrient agar and incubated at 28°C for 48 h. Individual colonies of bacteria which varied in shape and color were chosen and purified by streaking on nutrient agar. The bacterial isolates were identified using the VITEK 2 GN ID and VITEK 2 system. A total of 35 bacterial isolates were collected, purified, and identified to the species level. Of the 35 bacterial isolates, three isolates were selected for the current study, namely,E. hermannii, C. sedlakii, and P. putida isolates were cultured in nutrient broth medium to produce the bacterial biomass. The culture tubes  were incubated on orbital shaker  at 28°C overnight at 220 rpm. The biomass was harvested by centrifugation 10000 rpm for 10 minutes. The supernatants were collected for the production of silver nanoparticles.3)  at the concentration of 10−3 M (1%V/V) was added to the reaction vessels containing the bacterial isolate supernatants. The reduction of silver ions was carried out in the bright conditions for 24 hours. In addition, the blank test was also performed in the absence of silver nitrate. The bioreduction of (Ag+) ions was observed by monitoring changes of the color from light brown to dark brown and was observed among tested isolates and the absorption was periodically measured using UV-spectrophotometer  using quartz cuvette.Silver nitrate (AgNOUV-vis) spectrometer . The spectra were collected over a range of 200–1100 nm  as a function of reaction time by directly dipping the optical probe in the reaction vessel.The optical properties (absorbance) of colloidal sliver nanoparticles solutions were acquired with a , based on the data of an average of 70–100 particles. Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Klebsiella pneumonia ATCC 700603, Staphylococcus aureus ATCC 29213, and Staphylococcus epidermidis ATCC 12228 using the agar diffusion assay method [μL of sample nanoparticles solution (0.0002 mg). Briefly, bacterial lawns of bacterial test strains and hospital isolates were made on readymade Müller-Hinton agar and left to dry. The sterile discs were loaded with 20 μL silver nanoparticles solution containing approximately 0.0002 mg silver nanoparticles and then placed on Müller-Hinton agar nutrient agar plate with bacterial lawns and incubation at 37°C for 24 hours. All experiments were done in aseptic condition in laminar air flow cabinet. Zones of inhibition for control, SNPs, and antibiotics were measured in millimeters. The drug of choice for each tested strain was used for comparison, namely, gentamicin (P. aeruginosa), ceftriaxone (E. coli and K. pneumonia), and clindamycin (S. aureus and S. epidermidis). The zones of inhibition were measured, and the mean value was reported in millimeters. In order to test the efficacy of biosynthesized silver nanoparticles against real life pathogens, we tested the SHE silver nanoparticles against the major pathogens of Diabetic Foot Ulcer (DFU) isolated from diabetic foot patients recruited from University Diabetes Center in Riyadh, the capital city of Saudi Arabia, by using the agar diffusion assay method [ P. aeruginosa, or Gram-positive pathogens, namely, S. aureus, especially methicillin-resistant Staphylococcus aureus (MRSA). We investigated antimicrobial activities of biosynthesized silver nanoparticles against 22 isolates of P. aeruginosa, 21 isolates of S. aureus and 22 isolates of MRSA. We used gentamicin against P. aeruginosa isolates and vancomycin against S. aureus and MRSA isolates and were compared with our prepared silver nanoparticles. In addition, we studied the synergistic effect of combining silver nanoparticles and the antibiotic against the pathogenic organisms. The zones of inhibition were measured, and the mean values were reported in millimeters. The mean zone of inhibition ± SD was calculated and t-test was used to calculate P values among different treatment groups using SPSS software version 17.Antimicrobial activities of biosynthesized silver nanoparticles from SHE, S11P, and S5 isolates were tested against the following strains: Escherichia hermannii (SHE), Citrobacter sedlakii (S11P), and Pseudomonas putida (S5) were carried out using several methods such as (UV-vis) absorbance spectroscopy, Transmission Electron Microscopy (TEM), and zeta potential, as described below.The physicochemical properties of AgNPs obtained by different isolates, namely,UV-vis) and TEM. Such colors result from a SP resonance initiated by the interaction of the electric field of visible light with the confined electron gas within the particles, which caused collective oscillation of the conduction electrons with respect to the core [The reduction of Ag ions to Ag metal nanoparticles may be optically approved by color changes of the starting materials from colorless to brown. Color change observed is an indication of the formation of colloidal AgNPs . Howeverthe core , 32.λmax and SP band intensities, indicating a clear influence of the nature of isolates on these parameters. The spectra were recorded when both the color and absorption intensity of the colloidal samples stayed constant. It is clear from UV-vis spectroscopy is one of the most useful methods for characterizing the optical response of metal nanoparticles . Such a method has been proved to be quite sensitive to the formation of colloidal metal nanoparticles, due to their intense surface plasmon resonances (SPRs) . TypicalTo understand the surface morphology and to provide more information about the size of colloidal AgNPs prepared by different isolates, TEM investigation was conducted under similar conditions, as shown in ζ values varied in the range from −12 mV to −30.4 mV, depending upon the type of isolates applied. Thus, the different stability of colloidal AgNPs prepared by different isolates is also reflected by the changes in ζ values. Interestingly, the zeta potential value confirmed the high stability of the freshly prepared (mV0) colloidal mixture formed using S5 isolate (−30 mV), whereas the less stable particles were obtained with S11P and SHE isolates (−12.5 mV).Zeta potential can be used to gain further insights into the stability of the obtained colloidal AgNPs. The magnitude of zeta potential gives an insinuation of potential stability of colloid. It should be noted that the particles with zeta potential values more positive than +30 mV or more negative than −30 mV are considered to be stable . In contThe long-term stability of the colloidal AgNPs obtained by using different isolates, namely, SHE, S11P, and S5, was monitored over a longer time period by various techniques. The colloidal AgNPs were deliberately stored for this purpose in a closed glass vessel in dark environment. Afterwards, samples were taken at different predefined times  and were characterized by zeta potential measurements, UV-vis, and TEM to check the changes in zeta potential values, SP bands, size distribution, morphology, and so forth. The time-dependent changes using different isolates are summarized in τ)  were observed optically by a color change and estimating the precipitation time (τ) . SHE andζ) of the freshly prepared colloidal AgNPs by using SHE, S11P, and S5 are shown to be having ζ values of −20, −14, and −30.4 mV, respectively. The long-term stability of colloidal Ag nanoparticles was monitored spectroscopically by zeta potential technique, which indicates the changes in surface charge with time. Such method is widely used to control the stability of colloidal metal nanoparticles. The metal nanoparticles with a large positive or negative zeta potential tend to repel each other and they do not show any disposition to come together. Nevertheless, in case of low absolute zeta potential values, these particles aggregate and flocculate due to the absence of repulsive force which prevents such agglomeration. Zeta potential results , medium active nanoparticles producer isolate C. sedlakii (isolate S11P), and the least P. putida (isolate S5). Isolate SHE showed that best antimicrobial activity against four of the tested pathogens, namely, K. pneumonia, S. epidermidis, S. aureus, and E. coli., while isolate S11P showed the best antimicrobial activity only against P. aeruginosa  and silver nanoparticles and gentamicin combination with P values < 0.0001 in both cases. These results showed that silver nanoparticles treatment has better activity against some P. aeruginosa isolates compared with gentamicin antibiotic. It was found that silver nanoparticles showed the highest efficacy against five P. aeruginosa isolates (35 millimeters zone of inhibition) (22%). On the other hand, the highest efficacy observed for gentamicin (25 millimeters zone of inhibition) was observed against only one P. aeruginosa isolate (4.5%). In addition, a clear synergistic effect was observed between silver nanoparticles and gentamicin with zone of inhibition up to 44 millimeters. These results suggests the possibility of using silver nanoparticles and gentamicin combination to treat P. aeruginosa with lower probability of expected resistance, since no resistance so far has been reported against silver nanoparticles.Testing the antimicrobial efficacy against real pathogens showed that among S. aureus isolates, sizes of the zones of inhibition produced by silver nanoparticles ranged between 8 and 12 millimeters with mean ± SD value of 9.5 ± 0.9, while sizes of the zones of inhibition produced by vancomycin ranged between 10 and 11.5 millimeters with mean ± SD value of 10.4 ± 0.5. Whereas, sizes of the zones of inhibition produced by combining silver nanoparticles and vancomycin ranged between 11 and 13 millimeters with mean ± SD value of 11.9 ± 0.5. Statistical analysis showed that there is significant difference between treatment with silver nanoparticles and vancomycin against S. aureus isolates with P value of 0.001. Moreover, significant difference was observed between single treatments (silver nanoparticles or vancomycin) and silver nanoparticles and gentamicin combination with P values < 0.0001 in both cases. Also, a clear synergistic effect was observed between silver nanoparticles and vancomycin against DFU S. aureus isolates.Furthermore, among the tested 21 DFUP values of 0.346, while significant difference was observed between single treatments (silver nanoparticles or vancomycin) and silver nanoparticles and gentamicin combination with P values < 0.0001 in both cases. Our results surprisingly showed that silver nanoparticles produce successful antimicrobial effect against 5 MRSA isolates that were also resistant to vancomycin (MRSA-VRSA). Moreover, an obvious synergistic effect was observed between silver nanoparticles and vancomycin against MRSA isolates  position of AgNPs gave important information for particle size, shape, and size distribution. E. hermannii showed the best antimicrobial activity against tested pathogens due to its small stable AgNPs.Stability and antimicrobial activity of AgNPs found to be dependent on the nature of bacterial species. K. pneumonia, S. epidermidis, S. aureus, E. coli, and P. aeruginosa.Our AgNPs presented the best antimicrobial activity test againstOur AgNPs exhibited equivalent or enhanced antimicrobial activity compared with drug of choice.A clear synergistic effect between AgNPs and tested antibiotics was shown.Multidrug resistance is a rising problem in the treatment of infectious diseases. The wide use of broad-spectrum antibiotics has led to resistance to traditional antimicrobial agents for many bacterial human pathogens and has created a major threat to the global health care. AgNPs are considered as a potential source of novel antimicrobial agents, which offer numerous advantages such as broad-spectrum activity and lower tendency to induce resistance. In addition, broad-spectrum bioactivities of AgNPs make them potential agents in tackling serious problem of tumours and, particularly, multidrug resistant cancer cells. Moreover, AgNPs can be utilized in the diagnostics and treatment of different cancers. Therefore, this is an open area for many new studies in the cancer treatment with AgNPs. We also believe that in near future, AgNPs will have tremendous use as antiviral, antiprotozoal, and antiarthropod agents.


Antimicrobial resistance has been recognised as a serious global Public Health problem. Prevalence of Multiple-Drug-Resistant (MDR) organism carriage in Albania is largely unknown since no national surveillance system is in place and few publications are accessible in the literature.A 1-day point-prevalence-survey (PPS) screening for nasal methicillin-resistant Staphylococcus aureus (MRSA) and rectal MDR Gram-negative carriage was carried out at the high-dependency wards in the country’s only tertiary care hospital, in Tirana.E. coli  and Klebsiella pneumoniae  positive). Susceptibility to carbapenems (≥98 %), fosfomycin (90 %) and amikacin (70 + 20 % intermediate) was high but a high level of resistance to all other agents tested was noted. Non-fermenting Gram-negative bacilli were less commonly isolated {22 isolates: Acinetobacter baumannii (9); Pseudomonas aeruginosa (8) and Stenotrophomonas maltophilia (5)}.A total of 106 nasal and 104 rectal swabs were collected. 14.2 % of patients  were MRSA nasal carriers. Resistance to aminoglycosides and fluoroquinolones was common in these isolates (≥80 %) but no resistance was identified against glycopeptides, nitrofurantoin and the relatively newer agents, tigecycline and linezolid. Fifty Enterobacteriaceae isolates were cultivated from 33 of 104 screened patients (31.7 % [95 CI: 22.9–41.6 % 95 CI]). The prevalence of Extended Spectrum Beta-Lactamase (ESBL) production in Enterobacteriaceae was 41.3 % (95 CI: 31.8–51.4 %). The two more commonly isolated Enterobacteriaceae were Although a significant rate of MRSA carriage was identified, the main resistance challenge in Albania appears to be linked with Gram-negative organisms, particularly ESBL in Enterobacteriaceae. Antimicrobial resistance (AMR) is a serious, ever-growing, problem , 2. The Carriage and transmission of multidrug-resistant organisms (MDRO) have become a public health concern worldwide , 5. ThesAlbania is a small country in south-eastern Europe with a population of about 3,500,000 inhabitants. The University Hospital Centre ‘Mother Teresa’ of Tirana (QSUT) is the largest hospital in the country and the only tertiary-care referral centre for acute and critical patients. It incorporates 1555 beds, of which, around 110 are classified as intensive-care. Surveillance systems for Healthcare Associated Infections (HAIs) caused by MDRO have been established in most European countries; the highest proportions of resistant isolates have been reported in the Mediterranean countries . HoweverThis paper reports the results of a 1-day PPS to estimate prevalence of carriage of MRSA and MRGN in ‘Mother Teresa’ Hospital Tirana, Albania. The objectives of this survey were to: 1) assess the prevalence of nasal carriage of MRSA in QSUT; 2) assess the prevalence of rectal carriage of MRGN, 3) describe the susceptibility profiles of the isolates; 4) provide guidance on infection prevention and control measures to be undertaken.A delegation of 3 representatives from the Infection Control Unit in Mater Dei Hospital (MDH), Malta, visited QSUT in April 2015 in order to carry out a PPS. Patients with a higher risk of acquiring MDROs were targeted as the sampling cohort and included patients from Central Intensive Care Unit, high dependency wards, haematology, haemodialysis patients from the renal unit and long stay/chronic patients from medical and surgical wards throughout the hospital. Information on date of admission, diagnosis, previous and current antibiotic treatment including the type of antibiotic, was collected.Verbal consent was obtained from the patients before sampling. Each patient was sampled nasally, and rectally, using Amies Charcoal swabs (Transwab®MWE) pre-moistened with sterile saline. The total number of samples obtained was 106 nasal swabs and 104 rectal swabs; 2 patients accepted nasal, but refused rectal sampling.The swabs were inoculated onto various chromogenic plates. Initial growth vs. no growth was noted following an overnight incubation, with further work-up of positive specimens. Resistance thresholds determined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were used. Identification and sensitivity testing were performed on all the different organisms isolated, using the automated VITEK®2-compact system.Staphylococcus aureus as a negative control. For MRGN the organism strains used were: ATCC BAA1705—Klebsiella pneumoniae KPC, ATCC 700603—Klebsiella pneumoniae ESBL (SHV-18) and ATCC 27853-Pseudomonas aeroginosa as positive controls and ATCC 25922—Escherichia coli as a negative control.Quality control was performed on the sterile saline, catalase, coagulase and oxidase used, as well as the Agar media. For MRSA the following strains were utilised; ATCC 43300 (MRSA) as a positive control and ATCC 25932—The presence of MRSA was tested for on any pink colonies grown on a MRSA Select ™II chromogenic Agar by performing a sub-culture onto Blood Agar No.2 and incubation. The resultant growth was then subject to a Gram stain, as well as a catalase and slide-coagulase tests. The presence of DNAase was confirmed via the addition of hydrochloric acid to the DNAase Agar.Growth on each patient’s clinical specimen’s resultant ESBL and KPC Agar plates, and their respective MacConkey Agar plates, were compared. Further testing was performed for the detection of various types of enzymatic resistance mechanisms, on organisms with a resistant antibiogram profile.Stenotrophomonas maltophilia  could only be identified using the automated VITEK®2-compact with antibiotic sensitivity testing for co-trimoxazole, chloramphenicol, levofloxacin and colistin performed using Liofilchem® minimum inhibitory concentration (MIC) Test strips as per local protocol. The MICs were interpreted using EUCAST breakpoints for co-trimoxazole and Clinical and Laboratory Standards Institute (CLSI) breakpoints for the remaining 3 antibiotics tested.Escherichia coli and Klebsiella pneumoniae, and cefepime/cefepime and clavulanic acid and cefotetan/cefotetan and cloxacillin MIC Test strips for other members of the Enterobacteriaceae for confirmation of the presence of ESBL/AmpC.ESBL and AmpC screen kit were used in the case of The presence of carbapenemase production was elicited using the Modified Hodge Test (MHT) and confirmation of ertapenem MIC using Liofilchem®MIC test strips. If positive KPC/MBL and OXA-48 Confirm Kit were utilised as a means of identification of enzyme-type.Pseudomonas aeroginosa and Acinetobacter baumannii cultivated with raised MICs to carbapenems, were analysed for metallo-β-lactamase (MBL) production.Cases of All of the culture results, as well as the data gathered, were inputted on a central database (WHONET) and subject to an analytical process.n = 15) are shown in Table A total of 106 patients, from 16 wards, were screened for nasal carriage of MRSA, of whom 15 ] 8.1–22.3 %) were found to be positive for MRSA. In one particular ward 6 out of 9 screened patients were MRSA positive. The resistance profiles for MRSA isolates . The more commonly identified enzymes were ESBLs, which was detected in 43 of the Enterobacteriaceae isolates.n = 43) from 104 patients. The two more commonly isolated Enterobacteriaceae were E. coli (n = 28),  from 22 patients and Klebsiella pneumoniae 13 isolates  from 10 patients. The E. Coli isolates were all resistant to ampicillin but all susceptible to ertapenem, imipenem, meropenem and fosfomycin. The K. pneumoniae isolates were also resistant to ampicillin and ceftazidime. Two Enterobacter cloacae isolates were ESBL positive whilst the other 2 were ESBL negative but carbapenemase (KPC) and AmpC positive. One E. coli was only AmpC positive and one K. pneumoniae was both an ESBL, AmpC and carbapenemase (MBL) producer. The other Enterobacteriaceae isolates (n = 9) were: E. cloacae [n = 4 (3 patients)]; Citrobacter freundii [n = 3]; Morganella morganii [n = 1]; and Raoultella planticola [n = 1].A total of 104 patients were screened for rectal carriage of multidrug-resistant Gram-negative organisms. Some of these samples yielded more than one such organism. A total of 50 Enterobacteriaceae were isolated from 33 patients [31.7 % (95 CI: 22.9–41.6 %)]. There was heterogeneity in resistance mechanisms identified , Pseudomonas aeruginosa (n = 2) and Acinetobacter baumannii (n = 1). S. maltophilia were only tested for chloramphenicol, colistin, co-trimoxazole and levofloxacin. Of the five S. maltophilia, isolated from the 104 patients, 1 tested resistant to chloramphenicol and another to colistin.A total of 22 MDR Non-Fermenting Gram-negative bacilli were isolated. Unlike with MRSA and Enterobacteriaceae a different ward had the higher prevalence with P. aeruginosa isolates showed a high resistance to ciprofloxacin (75 %) and the aminoglycosides  amongst the isolated strains. Furthermore, all isolates were resistant to meropenem, aztreonam, ticarcillin and ticarcillin-clavulanate. A metallo-β-lactamase (MBL) carbapenemase, was detected in 6 of the 8 P. aeruginosa isolates. One of the P. aeruginosa isolates was resistant to all antibiotics tested except aztreonam, which was intermediate.The eight P. aeruginosa and A. baumannii. In 5 of the 9 A. baumannii isolates an MBL was detected. All A. baumannii isolates were susceptible to colistin, 3 were resistant to the carbapenems, ciprofloxacin and the glycopeptides and 2 were resistant to the carbapenems, ciprofloxacin and gentamicin .Figure S. aureus (including MRSA) was the single most frequently isolated pathogen [To our knowledge this is the first prevalence survey on MDRO carriage in patients admitted at QSUT. QSUT is the only reference centre in Albania for acute and critical patients. This survey enabled us to estimate, for the first time, the extent of nasal MRSA and rectal multidrug-resistant Gram-negative organisms (MRGN) carriage in this Albanian referral centre. In a previous study of HAIs carried out at QSUT, Gram-negative bacteria were the predominant pathogens, although pathogen .Our findings on MRSA carriage compare well with the findings from 26 Serbian hospitals, which had a prevalence of 11.8 % in screened patients . Other BIn addition, seven of the 15 MRSA strains showed resistance to aminoglycosides (gentamicin and tobramycin), fluoroquinolones (levofloxacin and moxifloxacin), erythromycin and clindamycin. This could possibly be related to a high use of fluoroquinolones and “macrolides and lincosamides“in Albania both in hospitals and possibly also in the community. Indeed it has been reported that the use of both has been increasing in the community .K. pneumoniae and 2 E. cloacae) that were resistant to ertapenem implying that CPE does not appear to be as yet a major issue in Albania. Carbapenems are not highly utilised in QSUT, thereby, these results are not surprising considering that there is a link between carbapenem use and resistance in Enterobacteriaceae [Our data suggest that MRGN carriage is a greater problem than MRSA. However, there were just three Enterobacteriaceae isolate  PPS, point prevalence survey; QSUT, The University Hospital Centre ‘Mother Teresa’ of Tirana; S. maltophilia, Stenotrophomonas maltophiliaAMR, Antimicrobial resistance; CLSI, Clinical and Laboratory Standards Institute; CPE, Carbapenemase-producing


Background and Aim. Identification of sensitive biomarkers to improve early diagnosis of HCC is needed. We aimed to evaluate serum midkine (MDK) as a biomarker for HCC diagnosis. Patients and Methods. 40 HCCs, 30 liver cirrhosis patients, and 30 healthy subjects were enrolled. Serum MDK using ELISA was measured in all included subjects. Results. Serum MDK was significantly elevated in HCC group compared to cirrhotic and healthy control groups (0.625 versus 0.15 and 0.125 ng/mL), respectively. No significant association was found between MDK and either BCLC stage, tumor diameter, tumor number, or AFP level. Receiver operating characteristic curve showed that best cutoff for MDK and AFP was 0.387 and 88.5 ng/mL, respectively. Area under the curve of MDK was significantly larger than that of AFP (0.941 versus 0.671). The sensitivity of MDK at 0.387 ng/mL for HCC diagnosis was significantly higher than that of AFP at cutoffs 20, 88.5, and 200 ng/mL , respectively. Sensitivity of MDK reached 93.3% in patients with AFP <20 ng/mL. Moreover, MDK at 0.387 ng/mL had significant better sensitivity than AFP at 20 ng/mL in distinguishing HCC from BCLC 0/A (90 versus 40%). Conclusion. Serum MDK might be a potential diagnostic marker for HCC particularity in its early stages. Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third most frequent cause of cancer-related death . In EgypHCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified because of the presence of underlying viral hepatitis or other liver diseases. The aim of surveillance is to obtain a reduction in disease-related mortality. This is usually achieved through an early diagnosis (stage migration) that, in turn, enhances the applicability and cost effectiveness of curative therapies .γ-carboxyprothrombin [The imaging test most widely used for surveillance is ultrasonography (US). Alpha-fetoprotein (AFP) is the most widely tested biomarker in HCC. However, AFP has a suboptimal performance as a serological test for surveillance for 2 reasons; firstly, fluctuating levels of AFP in patients with cirrhosis might reflect flares of HBV or HCV infection, exacerbation of underlying liver disease or HCC development . Secondlthrombin  and AFP-thrombin  were notMidkine (MDK), also known as neurite growth-promoting factor 2 (NEGF2), is a basic heparin-binding growth factor of low molecular weight. In humans, it is encoded by the MDK gene on chromosome 11 . It is aIn this study we aimed to investigate the diagnostic utility of midkine in patients with newly diagnosed hepatocellular carcinoma (HCC).The study protocol conformed to medical research ethical guidelines. After approval of the Research and Ethics Committee of Ain Shams University, Cairo, Egypt, in accordance with local research governance requirements, the study was carried out at HCC Clinic, Clinical Pathology, and Tropical Medicine Departments, Ain Shams University Hospitals during the interval between September 2013 and April 2014. An informed consent was taken from each participant before enrollment in the study.This study was conducted on 100 subjects who were divided into 3 groups; group 1 included 40 patients with newly diagnosed HCC, group 2 included 30 patients with liver cirrhosis (LC), and group 3 included age- and sex-matched apparently healthy subjects serving as a control group.Liver cirrhosis was documented by clinical assessment, laboratory findings, and evidence of liver cirrhosis upon abdominal ultrasound. The diagnosis of HCC was confirmed according to American Association for the Study of Liver Diseases (AASLD) guidelines in 2011 . PatientThe enrolled patients were subjected to full medical history taking, thorough clinical examination, and laboratory investigations including complete blood picture, complete liver and kidney profile, viral or autoimmune liver markers, serum alpha-fetoprotein by chemiluminescent immunometric technique, serum midkine by enzyme-linked immunosorbent assay (ELISA), and abdominal ultrasound. Only those in HCC group underwent further imaging in the form of abdominal triphasic spiral CT or magnetic resonance imaging as a part of HCC diagnosis. Child-Pugh classification was used to assess the severity of liver disease in patients with HCC and those with LC.Serum MDK was measured in all enrolled subjects using ELISA kit supplied by Glory Science . The assay is based on a double-antibody sandwich ELISA technique for the quantitative assay of human MDK in samples. In this technique, MDK binds to monoclonal antibody enzyme well which is precoated with human MK monoclonal antibody, making a solid phase antibody. Then MDK antibody is added and combines with Streptavidin-Horseradish Peroxidase (HRP) to form an immune complex. Following incubation, MDK is removed during a wash step and then substrates A and B are added to the wells and the color of the liquid changes into blue. The colored product is formed in proportion to the amount of MDK present in the sample. The reaction is terminated by addition of sulphuric acid. The concentration of MDK in the samples is then determined by comparing the  OD of the samples to the standard curve and values were reported as ng/mL.U test (Z). Kruskal Wallis test is applied for statistical comparison between more than two sets of data if one or both of them have a skewed distribution. Pearson correlation test (r) was used to investigate the correlation between 2 quantitative variables. Chi square (χ2) and Fisher's exact test (F) were used to examine the relationship between Categorical variables. The ROC was constructed to obtain the most sensitive and specific cutoff value for serum MDK in diagnosing HCC. Logistic Regression Model was used to combine information of MDK and AFP for diagnosis of HCC.Statistical analyses were conducted using SPSS 17.0 and MedCalc software. The significance level is 0.05. Data were expressed as mean ± SD for quantitative parametric measures in addition to Median Percentiles for quantitative nonparametric measures and both number and percentage for categorized data. The quantitative variables were analyzed by Mann-Whitney In this study, a total of 100 persons were recruited and enrolled including 40 newly diagnosed HCC patients with median age of 52 years old  and 10 were females (25%)), 30 patients with liver cirrhosis with median age of 48 years old  and 12 females (40%)), and 30 healthy individuals with median age of 45 years old  and 13 females (43.3%)). Hepatitis C virus (HCV) was the underlying etiology of liver cirrhosis in 38 (95%) and 29 (96.7%) patients in HCC group and liver cirrhosis group, respectively, while only 2 (5%) and 1 patients (3.3%) in HCC group and liver cirrhosis group had chronic hepatitis B virus infection, respectively. The HCC group included 20 patients with BCLC stages 0 and A (very early and early HCC), 10 patients with BCLC stage B (intermediate HCC) and 10 patients with BCLC stage C (advanced HCC). Child A class was found in 34 patients (24 in HCC group and 10 in liver cirrhosis group), Child B in 26 patients (16 in HCC group and 10 in liver cirrhosis group), and Child C in 10 patients with liver cirrhosis group.P < 0.001) and to the healthy control group . Meanwhile, however, the median values of MDK levels in the LC group were higher than that in the control group, yet not reaching significance  (P < 0.05) and healthy group   . Regardi< 0.001) .P = 0.001), while no significant association was found between serum MDK and BCLC stage . In the HCC group, there was no significant correlation between MDK with tumor diameter and number of tumor nodules . Also serum levels of MDK did not show any significant correlation with serum levels of AFP in all studied patients , while serum levels of AFP showed significant positive correlation only with tumor size but not with tumor number in the 40 HCC patients . In addition, on comparing the median values of serum MDK in child classes A, B, and C in CLD group patients using Kruskal Wallistest, there was no significant association found between serum MDK and child class .Patients with BCLC stage B/C had significant higher median AFP levels (300 ng/mL) when compared to those with stage 0/A (17 ng/mL) (P < 0.001) (ROC curve was performed for the best cutoff point to differentiate between HCC group and LC group using MDK and AFP. Area under the curve (AUC) for serum MDK was 0.941 (95% CI: 0.890–0.992) which was much higher when compared to that for AFP 0.671 (95% CI: 0.546–0.796) with significant statistical difference (< 0.001) . Accordi< 0.001) .P = 0.001, while the specificity of MDK cutoff value 0.387 ng/mL was only significantly higher than that of AFP at cutoff value 20 ng/mL   = 0.012) .P < 0.001) (To discriminate patients with early HCC (BCLC 0/A) from those with liver cirrhosis, the sensitivity of MDK at cutoff value 0.387 ng/mL was found to be much significantly higher when compared to that of AFP at cutoff values 20, 88.5, and 200 ng/mL  .P = 0.331), sensitivity (100% versus 92.5%), and specificity (96.7% versus 96.7%), respectively (P < 0.001 and 95% CI (0.889 to 0.994)  .It has been estimated that 70% to 90% of patients with hepatocellular carcinomas have an established background of chronic liver disease or cirrhosis, the major causes of which are HBV or HCV infection . In EgypWhen used as a diagnostic test, AFP levels at a value of 20 ng/mL show low specificity but fair sensitivity (60%); that is, AFP surveillance would miss 40%, whereas at higher cut-offs of 200 ng/mL the sensitivity drops to 22% with high specificity. Therefore, reducing the cutoff means that more HCCs would be identified, but at the cost of a progressive increase in the false-positive rate . ConsequP = 1.559), in contrast to serum AFP which was significantly elevated in the liver cirrhosis group when compared to healthy group . This means that the well-known nonspecific elevations of AFP in patients with liver cirrhosis were not significantly elicited with serum MDK increasing its specificity as a novel diagnostic marker for HCC.In this study, we found serum MDK was significantly elevated in patients with hepatocellular carcinomas compared with liver cirrhosis patients (median: 0.625 versus 0.15 ng/mL) and the healthy controls (median: 0.625 versus 0.125 ng/mL). In addition, serum MDK was not significantly higher in the liver cirrhosis group than that in healthy group . In addition, patients with advanced-stage hepatocellular carcinomas had significantly higher median AFP serum levels (BCLC B/C) than that of early-stage tumors (BCLC 0/A) . However, no significant correlation was found between serum MDK levels with tumor size, number or serum levels of AFP, and no significant association was found between serum MDK levels and BCLC stages.Serum AFP levels were found to be significantly correlated with larger tumor size in this study (P < 0.001) with high significant statistical difference. This means that the overall diagnostic performance of MDK for HCC diagnosis is much better than that of AFP.The best cutoff values for MDK and AFP to discriminate HCC cases from those with liver cirrhosis were 0.387 and 88.5 ng/mL, respectively, with sensitivities (92.5 versus 40%), specificities (83.3 versus 96.7%), and accuracies (88.5 versus 68.2%), respectively. Then through the analysis of the ROC, the AUC of MDK (0.941) was found to be much larger than that of serum AFP , we found that the sensitivities of MDK were significantly higher than those of AFP at all values , respectively, with similar specificities to AFP at cutoffs 88.5 and 200 ng/mL, while MDK had significantly higher specificity than that of AFP only at the value of 20 ng/mL (83.3 versus 53.3).Fifteen out of 40 HCC patients (37%) had low AFP (<20 ng); from those 15 patients, only 1 patient had MDK <0.387 ng/mL; this shows that MDK had an outstanding performance for distinguishing hepatocellular carcinomas from liver cirrhosis even in patients with AFP <20 with sensitivity reaching 93.3%. No one in the healthy control group exceeded MDK cutoff level 0.38 ng/mL and only 5 patients (16.7%) from liver cirrhosis group exceeded this threshold. On the other hand, 46.7% (14 of 30) of these patients were above the cutoff value of AFP (20 ng/mL). These indicate that MDK is a novel marker and superior to AFP with a lower false-positive rate in diagnosing and differentiating hepatocellular carcinomas from liver cirrhosis.P < 0.001).In terms of early detection and diagnosis of HCC, MDK at cutoff value 0.387 ng/mL showed a superior diagnostic performance to differentiate early stage HCC from patients with liver cirrhosis when compared to AFP at different cutoff values 20, 88.5, and 200 ng/mL   but the difference did not reach a significant level. Thus, combination of MDK and APF may be a promising strategy for early diagnosis of hepatocellular carcinomas in the future.Our results are close to those reported by Zhu et al. . That stIn conclusion, serum MDK may serve as a novel diagnostic tumor marker for the detection of hepatocellular carcinomas, particularly in patients with AFP <20 ng/mL and/or at an early stage. Further studies with larger population are needed to justify its implementation in clinical practice.


Job stress and emotional exhaustion have been shown to have a negative impact on the helping professional. The development and causal relations of job stress and emotional exhaustion are rather unclear in the chiropractic profession. The objective of this study is to understand the main sources of occupational stress and emotional exhaustion among doctors of chiropractic.Analysis of the written responses to web-based open-ended questionnaire was performed using an interpretive research methodology. Additionally, cross tabulation and Chi square statistical tests were conducted to match and couple the demographic data with the categorical themes.Fourteen professional stress categories emerged from the 970 completed surveys. “Managed Care Organization regulation”, “Managed Care reimbursement” and “Scope of Practice Issues” were the most common stressors that negatively influenced chiropractors’ professional and personal lives. The results of the categorical analysis suggests that age, marital status, number of years in practice and location of practice may have an influence on the category of stress reported by chiropractors.The qualitative approach revealed common, conventional and culture-specific job stressors in doctors of chiropractic. Notably, these findings suggest an association between third-party payer influences (increased regulation/decreased reimbursement) with that of increased job stress. Further research will be undertaken to refine the stress and satisfaction parameters and address stress interventions. Occupational stress and emotional exhaustion (EE) are extensive problems for health-care workers –4. OccupAccumulated research on occupational stress has generated a wealth of knowledge about the stress process and how stress affects workers in a wide variety of jobs –15. McMaAs changes in the political sector of the health care arena continue to mount, and new socioeconomic trends occupy the environment of health care, the nature and construct of occupational stress and EE may continue to develop as a serious threat to workers’ well-being , 20–23. What factors do you feel influence the levels of occupational stress and emotional exhaustion in the chiropractic profession?’A demographic survey including six socio-demographic categorical questions and one open-ended question was emailed (July 2013) to a randomized and convenience sample of DCs whose email addresses were included in the database of a leading chiropractic-marketing agency . The invlow fees, too much paperwork, too much government regulation, deny-minded IME interfering with care, staff training, high expenses” includes many items that could fall in one (Business & Administration) or more (MCO regulation and reimbursement) categories. Categories were not preconceived and were named using respondents’ own terminology where possible. The principle investigator (PI) read all of the statements in the initial sample and carried out this analysis on two additional separate occasions. The initial analysis generated almost identical sets of categories. A set of 14 categories was composed based directly on the respondents’ statements.A mixed methods approach was used to explore respondents’ perceptions of occupational stress and EE. The qualitative portion of this research design used content analysis , 26, indThe quantitative analysis integrated summaries of the categorical themes that were obtained after the open-ended responses, with similar themes grouped together. Descriptive statistics involving the frequency and percentage summaries were conducted to determine the number of respondents that chose each of the categorical themes. Cross tabulation(s) were conducted to match the demographic data of gender, age, years in practice, marital status, current professional status, and location of practice with the categorical themes of the open-ended responses. Chi square statistical test(s) were conducted to determine if the demographic data was significantly related to, or differed with, the categorical themes of the open-ended responses. A level of significance of 0.05 was used in the statistical analysis. During the study, several methods were used to ensure the data trustworthiness  as outlined by Zhang . All anaMost of the respondents were solo-practitioners and practicing in the United States. Additionally, most of the respondents were male and were married. It was observed that the age of those that answered the open-ended questions were between 31 and 60 years old.The open-ended question was examined for common themes. The most-common responses were Managed Care Organization (MCO) Regulation (33 %), MCO Reimbursement (26.8 %), and Scope of Practice Issues (21.3 %). There were also significant numbers of responses for Business and Administrative (16.4 %), Public Perception / Public Acceptance (16.1 %), Self–Perception / Purpose (11.2 %), and Economy / Money (10.3 %).In the 14 categorical themes of response, it was observed that many of the respondents practiced chiropractic in California, Colorado, Connecticut, Florida, Georgia, Illinois, New Jersey, New York, North Carolina, Ohio, Pennsylvania, and Texas. The percentage distribution of gender, the number of years in the professions and the practice location found in this study was reflective of current industry data , 30.There were a total of 970 analyzed open-ended responses out of the 1149 total respondents  and MCO Reimbursement . Scope of Practice Issues  and Public Perception / Public Acceptance  and Business and Administrative  were also noted as significant stressors across both genders. The same trend was observed in those DCs that were currently married. The age of the participants and the number of years in their profession was spread fairly evenly. When investigating the top three stressors that influence their professional lives, those DCs aged 31 to 40, 41 to 50, and 51 to 60 years old respectively, believed that MCO Regulations , MCO Reimbursement , and Scope of Practice  had the most noteworthy negative impact. Interestingly, DCs that said MCO Regulations, MCO Reimbursement, and Scope of Practice Issues were the most influential stressors in practice – were also those that had most years in active practice (20 -30+ years in practice). Of the 311 respondents that noted MCO Reimbursement as a significant stressor, 208 were sole-practitioners and 69 were in group practice. Of the 384 respondents that noted MCO Regulations as a significant professional stressor, 262 were sole-practitioners and 74 were in group practice. Of the 247 DCs that noted Scope of Practice, 167 were sole-practitioners and 48 were in group practice.Collectively, when investigating the top three stressors that influence their professional lives, DCs noted MCO Regulations, MCO Reimbursement, and Scope of Practice Issues, the State or U.S. territory the respondents were practicing chiropractic was mostly from California, New York, and Pennsylvania. Of the 311 respondents that noted MCO Reimbursement, 37 were from Pennsylvania, 35 from California, and 33 from New York. Of the 384 respondents that noted MCO Regulations, 51 were from Pennsylvania, 41 from New York, and 35 from California. For the 247 respondents that noted Scope of Practice Issues, 33 were from California, 18 from New York, and 12 from Pennsylvania.2 (1) = 3.93, p = 0.05), Patients (X2 (1) = 35.35, p = 0.02), Public Perception / Public Acceptance (X2 (1) = 4.76, p = 0.03), and Working too hard (X2 (1) = 6.35, p = 0.01). Chi-square test also showed that age was significantly related with the responses of business and administrative (X2 (5) = 11.68, p = 0.04), patients (X2 (5) = 18.88, p <0.01), self-perception (X2 (5) = 15.99, p = 0.01), and working too hard (X2 (5) = 16.90, p = 0.01). Additionally, chi-square test also showed that the number of years in practice was significantly related with the responses of MCO regulation (X2 (6) = 12.68, p = 0.05), patients (X2 (6) = 27.07, p <0.001), other (X2 (6) = 15.12, p = 0.02), and working too hard (X2 (6) = 22.18, p <0.001); and that marital status was significantly related with the responses of patients (X2 (4) = 17.72, p <0.001), economy (X2 (4) = 13.04, p = 0.01), and working too hard (X2 (4) = 11.60, p = 0.02). Collectively, this indicates that the two gender groups, the six age groups, the seven categories of years in practice and the five categories of marital status have significant different responses in the open-ended responses. As per the various DC working characteristics, the results of the chi-square test showed that current professional status was significantly related with the responses of Intra-Professional Stress (X2 (4) = 14.94, p = 0.01), Patients (X2 (4) = 26.11, p <0.001), and Student Loan Debt (X2 (4) = 12.40, p = 0.02). Additionally, location of practice (Table X2 (3) = 9.77, p = 0.02), MCO regulation (X2 (3) = 13.44, p <0.001), and self-perception (X2(3) = 9.89, p = 0.02). Collectively, this indicated that the five categories of current professional status and the four categories of location of practice have significant different responses in the open-ended responses of Intra-Professional Stress, Patients, and Student Loan Debt, and MCO Reimbursement, MCO Regulation, and Self-Perception / Purpose, respectively.The results of the chi-square test showed that gender was significantly related with the responses of MCO Regulation  on DCs’ practice life; by means of reducing resources and increase demands, as outlined in the control-stress model [the frustration with the insurance companies”. Complaints of constantly getting denied, the extremely low reimbursement (gets lower every year), the raising of co-pays to make patients not want to come in appear to be overwhelming the modern day DC. These findings are consistent with much of the current occupational stress research [The primary aim of the current study was to examine the perceptions of occupational stress among a representative sample of chiropractors in the US. This mixed methods approach, with emphasis on the qualitative analysis, generated three main categories and 14 subcategories representing the perceived occupational stressors among DCs. Overall, the results showed that the most of the participants believed that MCO regulation, MCO reimbursement, and Scope of practice issues were the most common stressors that negatively influenced their professional and personal lives. Interestingly, scope of practice amongst DCs is highly variable –34 in thss model  and job-ss model , 11. Howresearch –22, 27; Similar precursors/processes to occupation stress and EE have been observed in a comprehensive group of health professionals , 35–37 –As the content analysis progressed, a conceptual pattern amongst the participants began to unfold. It appears that many of the participants agreed – Chiropractic’s lack of internal consensus and legitimacy  inhibits chiropractic’s ability to keep up with rapidly changing events. Further, participants repeatedly noted/suggested that in order for the chiropractic profession to progress, that is keep up with external health care events, e.g., the Affordable Care Act, Health Care Education Reform Act, etc., the profession would needs to come to some modicum of internal consensus. Internal consensus will be needed if the profession is going to achieve cultural authority . KeepingThe limitation of the categorical analysis involving determining the relationship between the demographics with the categorical themes of open-ended responses is that causality cannot be determined. Also, finding a significant relationship between two variables with a correlation coefficient does not take into account the possibility of other variables playing a part. In addition, the direction (positive or negative) of the relationship and the strength of the relationship  cannot be determined with a chi-square test. The variables of demographic and categorical themes of open-ended responses are categorical variables. Thus, correlation test cannot be conducted. The analysis merely determined the relationship between variables by investigating whether there is significance different in the categorical responses according to the results of the chi-square analysis.The findings from this current study add to a continuous dialog on the unique causes of stress, emotional exhaustion and occupational stress for chiropractic professionals. These findings in this study add to the notion of directional association between third party payer influences (increased regulation/decreased reimbursement) with that of increased job stress. Further research will be undertaken to refine the stress and satisfaction parameters and address stress interventions.


I. frutescens (MEIF) using different experimental animal models. Anticonvulsant activity of the single dose of MEIF  was evaluated in maximal electroshock- (MES-), pentylenetetrazole- (PTZ-), and isoniazid- (INH-) induced convulsions models in rats. The levels of γ-amino butyric acid (GABA), glutamate, GABA-transaminase (GABA-T) activity and oxidative stress markers were measured in pretreated rat's brain homogenate to corroborate the mechanism of observed anticonvulsant activity. MEIF  protected the animals in all the behavioral models used. Pretreatment of MEIF  and diazepam  to the animals in INH-induced convulsion model showed 100% and 80% protection, respectively, as well as significant restoration of GABA and glutamate level in the rat's brain. MEIF and vigabatrin  reduced the PTZ-induced increase in the activity of GABA-T (46%) in the brain. Further, MEIF reversed the PTZ-induced increase in lipid peroxidase (LPO) and decrease in reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. The findings of this study validate the anticonvulsant activity of I. frutescens.The present study was carried out to evaluate the anticonvulsant activity and probable mechanism of action of the methanol root extract from  Abelmoschus angulosus Wall. ex Wight & Arn. , Allium sativum L. (Amaryllidaceae), Cinchona officinalis L. (Rubiaceae), Plumbago zeylanica L. (Plumbaginaceae), and Egletes viscosa (L.) Less. (Asteraceae) are used since time immemorial for the treatment of epilepsy in the Indian system of traditional medicine [Epilepsy is the result of abnormal, hypersynchronous neuronal activity  , affectimedicine .Ichnocarpus frutescens (L.) R. Br. (Apocynaceae) is a woody climber, distributed in India, ascending to an altitude of up to 4000 ft above sea level [ I. frutescens root is one of the important ingredients of the Ayurvedic formulations “Ashwagandharishta” and “Swalpachaitasa Ghrita,” which are indicated for the treatment of epilepsy and other ailments [α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)-α-amyrin [α-amyrin, lupeol, β-sitosterol, friedelin, epi-friedelinol [β-D-glucopyranoside [ I. frutescens (MEIF) using MES-, PTZ-, and INH-induced convulsion models in rats.ea level . Traditiea level –12. I. failments . The impα-amyrin , α-amyriedelinol , apigeniedelinol , kaempfeedelinol , quercetranoside . PharmacAmino acid transmitters particularly play an important role in the pathogenesis of epileptic conditions , 20. It Pentylenetetrazole, isoniazid, gamma aminobutyric acid, glutamate, diazepam (D-907), phenytoin (PHR1139), and vigabatrin were purchased from Sigma Ltd., USA. ELISA kit  was used for the estimation of GABA-T activity.Plant material was collected in the month of December (2011) from the medicinal garden of Rajiv Gandhi South Campus, Banaras Hindu University, Barkachha, Mirzapur, UP, India. The identification of the plant material was done by Dr. Subir Bandyopadyay at the Botanical Survey of India, Howrah, West Bengal, India (plant identification letter: CNH/104/2012/Tech. II/950). For future reference a voucher specimen (number PRL-02) of the plant material has been deposited in the Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi. I. frutescens were separated from the aerial parts and shade-dried until a constant weight was obtained. The roots were then pulverized into coarse powder and sieved by 20# sieve. The coarse powdered drug (475 g) was extracted with methanol (2.0 l) by cold maceration process for 10 days. After 10 days the content was filtered and the filtrate obtained was concentrated under reduced pressure in rotary evaporator  below 60°C. Methanol extract of I. frutescens (MEIF) (5.26% w/w) obtained was kept in desiccator for several days to completely remove the traces of solvent.Roots of ad libitum. Each animal was used for one seizure experiment only. Fasting of the animals (with free access to water ad libitum) for 18 h prior to the experiment was done in all the tested anticonvulsant models.Inbred Charles Foster rats (120–150 g) of either sex were obtained from the Central Animal House of Banaras Hindu University, Varanasi. The experimental study was performed after receiving necessary approval from the Institutional Animal Ethical Committee (IAEC), Institute of Medical Sciences, Banaras Hindu University, Varanasi (Dean/13-14/CAEC/193). All the animals were housed and maintained under standard laboratory conditions in polypropylene cages at constant room temperature (22.0 ± 3.0°C), relative humidity (50 ± 10%), and 12 : 12 h dark and light cycle. The animals were allowed to acclimatize to the environment of the laboratory for 7 days before the commencement of experiments. Animals were fed with commercial rat feed  and watern = 5) and rats were observed at 0, 30, 60, 120, 180, and 240 min and then once a day for the next 14 days for any signs or symptoms of toxicity or abnormalities. The number of rats that survived at the end of the study period was recorded [The acute oral toxicity study of MEIF was performed according to the Organization for Economic Co-Operation and Development (OECD)—425 guidelines. Single dose of MEIF 2000 mg/kg, p.o., was administered in 24 h fasted rats (recorded .n = 6). Group I (negative control) served as untreated group and received only carboxymethyl cellulose . Group II (standard treated group) received single dose of phenytoin , whereas Groups III, IV, and V (MEIF treated groups) received the single dose of the MEIF 100, 200, and 400 mg/kg, p.o., respectively. All the animals received electric shock stimulation 30 min after the treatment with standard drug and graded dose of MEIF. After electrical stimulation, the occurrence and duration of HLTE and incidence of mortality were noted. The criterion for the evaluation of anticonvulsant activity is the ability to prevent HLTE or reduction in the duration of HLTE [The maximal electroshock seizure (MES) was tested in animals through transauricular electrodes attached bilaterally to the animal ear. Electroconvulsive shock producing an alternating current stimulus  was delivered through ear-clip electrodes to induce hind limb tonic extension (HLTE) in rats. The electrodes were moistened with a drop of electrolyte solution prior to delivery of the electroshock . Animals of HLTE .n = 6). Group I  received only vehicle . Group II (negative control) was administered with INH  only. Group III (standard treated group) received standard drug diazepam . Groups IV, V, and VI (MEIF treated groups) were administered with MEIF 100, 200, and 400 mg/kg, p.o. Convulsion was induced to all the animals (except Group I) by single dose administration of INH  after 30 min of the treatment with the MEIF and the standard drug. All the animals were carefully monitored for 30 min for the occurrence of convulsions. The latency of convulsions was recorded and the percentage protection was calculated [In INH-induced convulsion model, animals were randomly divided into six groups comprising six animals in each group ((1) Chromatographic Estimation of GABA and Glutamate in Whole Brain. GABA and glutamate levels were estimated in rat brain using high performance liquid chromatography . Briefly, brain tissues were homogenized in 0.1 M perchloric acid containing 4 mM sodium metabisulphite solution (30 μL per 10 mg of tissue) [μm). Pellet and filtered supernatant were stored separately in Eppendorf tubes at −80°C until the analysis. Concentrations of GABA and glutamate were measured using precolumn derivatization with o-phthalaldehyde (OPA) and fluorescence was detected [μL filtered supernatant with 6 μL OPA and injecting this mixture into the solvent stream of the HPLC system, 2 min later. Separation of OPA-GABA and OPA-glutamate was carried out on a reversed phase 3.9 × 150 mm column  at 35°C using a binary gradient system of mobile phases A and B  at a flow rate of 0.5 mL/min. Fluorometric detection was performed with a fluorescence detector  at excitation and emission wavelengths of 360 and 450 nm, respectively. This procedure allowed the quantification of GABA and glutamate levels by linear regression using external standards . Protein content was determined using the residual pellet according to a modified version of Bradford's method [μg/mg protein. tissue) . The resdetected . Derivats method . GABA ann = 6). Group I  received vehicle  only. Group II (negative control) received PTZ , whereas Group III (standard treated group) received vigabatrin . Groups IV, V, and VI (MEIF treated groups) received MEIF 100, 200, and 400 mg/kg, p.o., respectively. Convulsion was induced in all the animals (except Group I) by single dose administration of PTZ  after 30 min of the treatment with the extract or standard drug. Animals which showed no convulsions within 30 min were considered as protected and the percentage protection in each group was calculated. In unprotected animals, the latency of the first convulsion was recorded [In PTZ-induced convulsion model, the animals were randomly divided into six groups with six animals in each group  Estimation of GABA-T Activity and Oxidant Stress Markers. 500 mg of rat brain tissue was taken and rinsed with phosphate buffer solution . Brain tissue was homogenized in 5.0 mL of PBS and stored overnight at −20°C. The homogenates were centrifuged for 5 min at 5000 ×g maintaining the temperature between 2 and 8°C. The supernatant obtained was assayed for the estimation of both GABA-T activity and oxidant stress markers.(1.1) Estimation of GABA-T Activity. The supernatant of brain homogenate was assayed for GABA-T activity spectrophotometrically at 450 nm using commercially available ELISA kit . GABA-T was expressed as pg/mg protein. (1.2) Estimation of LPO Activity. Lipid peroxidation was measured and expressed in terms of malondialdehyde (MDA) as per the method of Liu et al. [n-butanol and pyridine mixture (15 : 1) and vortexed vigorously. The organic layer was separated after centrifugation at 4000 rpm for 10 min. Absorbance of organic layer was measured by using spectrophotometer at 532 nm and the concentration was expressed as nmol MDA/g tissue.u et al. . 1.0 mL (1.3) Estimation of GSH Activity. Reduced glutathione activity was measured as per the method of Sedlak and Lindsay [μg GSH/g of tissue. Lindsay . Trichlo(1.4) Estimation of SOD Activity. SOD activity was determined as per the method of Kakkar et al. [μM phenazine methosulphate, 0.3 mL of 300 μM nitroblue tetrazolium (NBT), and 0.8 mL of distilled water. This mixture was added with 2.0 mL of 780 μM NADH solution and incubated at 30°C for 60 sec. After incubation, the reaction was terminated by the addition of 1.0 mL of glacial acetic acid. The reaction mixture was then shaken vigorously with 4.0 mL of n-butanol and later centrifuged at 3000 rpm for 5 min. The butanol layer was separated and the color intensity was measured at 560 nm against n-butanol. A system devoid of enzyme served as control. SOD activity in the homogenate was expressed as unit of SOD activity/g of tissue.r et al. . Brain h(1.5) Estimation of CAT Activity. Catalase activity was determined according to the method described by Aebi [μL) was added to a cuvette containing 2.0 mL of phosphate buffer (pH 7.0) and 1.0 mL of 30 mM H2O2. Catalase activity was measured by using spectrophotometer at 240 nm for 1 min and expressed as unit of CAT activity/g of tissue. by Aebi . Brain hn = 6). The analysis of variance was done by using one-way ANOVA followed by Tukey's posttest for multiple groups comparison. The difference was considered to be significant when P < 0.05. GraphPad Prism (version 5) software was used for all statistical analyses.All the results were expressed as mean ± SEM  and phenytoin  exhibited significant reduction in the duration of tonic convulsion when compared to negative control group. However, when compared to phenytoin  treated group, MEIF  exhibited no significant difference in reduction of the duration of HLTE, thus revealing that the potency of the extract is comparable to that of phenytoin .INH  exhibited HLTE in all the six animals of negative control group. Diazepam  produced 100% protection against the convulsion induced by INH. However, MEIF  exhibited significant protection (up to 80%) and increased the latency of tonic convulsion as compared to negative control group .Rats administered with INH  showed significant reduction in the level of GABA by 69% and elevation in the level of glutamate by 59% in the brain homogenate when compared to normal control rats. Diazepam  and MEIF  produced significant recovery in the level of GABA, whereas the level of glutamate was observed to decrease significantly. MEIF  did not produce any significant activity in recovering the level of GABA and reduction in the level of glutamate .Animal groups treated with MEIF  and vigabatrin  showed significant increase in the latency of tonic convulsions induced by PTZ  as compared to negative control group. The percentage protection was observed to be as high as up to 66% and 100% when the rats were, respectively, treated with MEIF and standard drug vigabatrin .Rats administered with PTZ  showed significant increase in the level of GABA-T enzymatic activity by 46% as compared to normal control group. Treatment of the animals with standard drug vigabatrin  and MEIF  produced a significant reduction in the level of GABA-T enzyme when compared to negative control group. However, the lower dose of MEIF  showed no significant effect in the reduction of enzyme activity .The results in The objective of the present study was to investigate the protective effect of MEIF  against physical and chemical induced convulsion in experimental rat models. MEIF  dose-dependently reduced the convulsions in MES treated rats. Pretreatment of MEIF  reversed INH-induced decrease and increase in the level of GABA and glutamate in the rat brain, respectively. MEIF  attenuated the PTZ-induced increase in the activity of GABA-T in the rat brain. Further, MEIF  reversed the PTZ-induced increase in the level of LPO and decrease in GSH, CAT, and SOD levels. I. frutescens is an important ingredient of many Ayurvedic formulations, commonly used for the treatment of epilepsy along with other diseases, but has not been investigated scientifically. In MES-induced convulsion model, neither phenytoin nor MEIF  protected the animal completely, but a significant reduction in the duration of tonic convulsion was observed. Lower dose of MEIF  showed no significant reduction in the duration of convulsion in MES exposed animals. MES induces seizure particularly due to the spread of stimulus throughout the body and anticonvulsant drugs that block the effect of MES act by blocking the seizure spread [Root ofe spread . Thus, tA receptor [Epilepsy is a condition of spontaneous recurrent seizures having a close relation with the GABAreceptor . Seizurereceptor . GABA anreceptor . Glutamireceptor . Drugs tA receptor complex [As MEIF  reversed the INH-induced decrease in the GABAergic activity, we further investigated the effect of MEIF  in PTZ-induced animal model of convulsion. It is well reported that PTZ induces convulsion through antagonism at the picrotoxin-sensitive site of GABA complex . As a re complex .α-ketoglutarate leading to the depletion in the level of GABA [In the present study, standard drug vigabatrin  showed complete protection against PTZ-induced convulsion while MEIF  showed dose-dependent effect against PTZ-induced convulsion. GABA-T is the primary catabolic enzyme in the mammalian brain that catalyzes the transfer of amino group from GABA to  of GABA . PTZ sig of GABA , 44. Thuα-amyrin and ursolic acid have been isolated from MEIF and standardized by HPTLC [ I. frutescens is also reported to contain quercetin along with other phenolics [ in vitro study [α-amyrin (triterpenoid) retains a balance between excitatory and inhibitory neurotransmitters in convulsion [Literature survey reveals that MEIF is a rich source of triterpenoids, phenolics, and steroids . Recentlby HPTLC . I. fruthenolics . It has ro study  and protro study . Quercetro study . Moreovenvulsion . Phenoli I. frutescens could be a potential source in the management of convulsion.Hence, from the present study, it can be concluded that MEIF  showed anticonvulsant activity through modulating GABAergic system and oxidative stress in the rat's brain which can be predicted due to the presence of different category of phytoconstituents . Therefore, roots of


Heart failure (HF) patients are at risk for structural brain changes due to cerebral hypoperfusion. Past work shows obesity is linked with reduced cerebral blood flow and associated with brain atrophy in healthy individuals, although its effects on the brain in HF are unclear. This study examined the association among body mass index (BMI), cerebral perfusion, and brain volume in HF patients.p < .05). BMI also interacted with cerebral perfusion to impact total gray matter volume, but this pattern did not emerge for any other MRI indices (p < 0.05).Eighty HF patients underwent transcranial Doppler sonography to quantify cerebral blood flow velocity of the middle cerebral artery (CBF-V of the MCA) and brain magnetic resonance imaging (MRI) to quantify total brain, total and subcortical gray matter, white matter volume, and white matter hyperintensities. Body mass index (BMI) operationalized weight status. Nearly 45% of HF patients exhibited a BMI consistent with obesity. Regression analyses adjusting for medical variables, demographic characteristics, and CBF-V of the MCA, showed increased BMI was associated with reduced white matter volume (Our findings suggest increased BMI negatively affects brain volume in HF, and higher BMI interacts with cerebral perfusion to impact gray matter volume. The mechanisms for these findings remain unclear and likely involve multiple physiological processes. Prospective studies are needed to elucidate the exact pattern and rates of brain changes in obese HF persons. Heart failure (HF) is associated with adverse medical outcomes, including greater risk of mortality and rehospitalization . Past fiCerebral hypoperfusion and the resulting ischemia have been proposed to be the most significant contributors to adverse brain changes in patients with HF , 7–9. SuObesity affects up to 40% of HF patients, and has adverse effects on brain volume in this population –22. IndeDespite these findings, no study to date has examined the association among body mass index (BMI), cerebral perfusion, and brain volume in persons with HF. The purpose of the current study was to examine the independent association between BMI and brain volume in older adults with HF. We then sought to determine whether elevated BMI and decreased cerebral perfusion interact to exacerbate brain volume reductions in this population.This sample consisted of 80 persons with HF from an ongoing study of neurocognitive outcomes in HF. Strict inclusion/exclusion criteria were chosen for entry into the study. Specifically, the participants were between the ages of 50–85 years of age, native English speakers, and had an established diagnosis of New York Heart Association (NYHA) class II, III, or IV at the time of enrollment. Exclusion criteria included history of significant neurological disorder , head injury with more than 10-minutes loss of consciousness, severe psychiatric disorder , history of substance use, and renal failure. Participants for the current study were also excluded for any contraindications to magnetic resonance imaging (MRI), such as cardiac pacemaker. Participants averaged 68.23 (SD = 8.58) years of age, and 35.0% of them were women. Medical record review revealed that the current sample exhibited an average left ventricular ejection fraction (LVEF) of 42.99 (SD = 13.32). See Table Whole-brain, high-resolution 3D T1-weighted images  were acquired on a Siemens Symphony 1.5Tesla scanner for morphometry analysis. Twenty-six slices were acquired in the sagittal plane with a 230 × 100 mm field of view. The acquisition parameters were as follows: Echo time (TE) = 17, repetition time (TR) = 360, acquisition matrix = 256 × 100, and slice thickness = 5 mm. Whole-brain T2 and FLAIR images were also acquired to quantify WMH. For the T2-weighted images, twenty-one 5-mm thick slices were acquired with a 230 × 100 mm field of view with TR = 2910 and TE = 134. For the FLAIR images, twenty-one 5-mm slices were acquired with TR = 8500, TE = 115, and FOV = 220 × 75.http://surfer.nmr.mgh.harvard.edu). Detailed methodology for regional and total volume derivation has been described in detail previously [Morphometric analysis of brain structure was completed with FreeSurfer Version 5.1  volume was derived by a three-step operator-driven protocol that has been described in detail previously , 29. BriTranscranial Doppler ultrasonography through an expanded Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol  was usedParticipant demographic and medical characteristics were ascertained through medical record review and self-report. See Table The Kent State University and Summa Health System Institutional Review Boards approved the study procedures and all participants provided written informed consent prior to study enrollment. All study procedures comply with the Declaration of Helsinki. For all participants, a medical chart review was performed and height and weight were measured. HF patients then underwent TCD and brain MRI.A square root transformation was applied to WMH to correct for a positively skewed distribution. Separate hierarchical regression models were used to examine the independent effects of BMI and CBF-V of the MCA on structural brain indices . However, to limit the number of analyses and preserve power, for each volumetric index, one regression model that included both CBF-V of the MCA and BMI was performed to determine the effects of each of these variables on the MRI variables. Intracranial volume, as well as medical and demographic characteristics was entered in block 1. They included age, sex , years of education, LVEF, diagnostic history of hypertension, diabetes, sleep apnea, myocardial infarction, and depression . These medical and demographic variables were included as covariates in light of their known influence on neurocognitive outcomes in older adults with HF. CBF-V of the MCA was then entered as a block 2 variable and the continuous BMI variable was entered in block 3 to determine the incremental predictive validity of BMI and cerebral perfusion on brain volume in HF. Moderation analyses using hierarchical regression models were conducted to determine the synergistic effects of BMI and cerebral perfusion on the same volumetric indices listed above. Intracranial volume, BMI, and CBF-V of the MCA were transformed to z-scores and individually entered in block 1. The cross product of BMI and CBF-V of the MCA was computed and entered in block 2.r(78) = −.22, p = .05).The sample mean BMI was 29.89 (SD = 6.68). By common categorization, 25.0% of the participants fell within the normal range (BMI = 18.5-24.9), 33.8% were overweight (BMI = 25 to 29.9) and 41.3% of the sample exhibited a BMI consistent with obesity (BMI ≥ 30). BMI groups did not differ in age, sex, education, LVEF, NYHA class, and frequency of diagnostic history of diabetes, myocardial infarction, and depression. In contrast, sleep apnea and hypertension were more common among the obese persons than among overweight and normal weight participants. See Table p < .05 for all). See Table p = .03). Significant findings for CBF-V of the MCA were not observed for any of the other brain volume indices (p > .05), although all values were in the expected positive direction .Models containing medical and demographic characteristics were associated with total brain volume, total gray matter volume, subcortical gray matter volume, cortical white matter volume, and WMH (p = .04) and strong trends for reduced subcortical gray matter volume  and smaller total brain volume . No such pattern emerged for total gray matter volume or WMH (p > .05 for each).Hierarchical regression analyses controlling for medical and demographic characteristics and CBF-V of the MCA revealed that elevated BMI demonstrated a significant association with decreased white matter volume . However, no interactive effects between BMI and CBF-V of the MCA emerged for total brain volume , subcortical gray matter volume , cortical white matter volume , or WMH .Moderation analyses using a hierarchical regression model showed a significant interaction between BMI and cerebral perfusion on total gray matter volume  gene [The current study suggests that elevated BMI is independently associated with reduced structural brain volume in older adults with HF. There are several possible mechanisms for such findings. First, obesity promotes vascular risk factors  that are known to produce structural brain changes, even in healthy adults , 34. In TO) gene . Future TO) gene .The current study suggests that decreased cerebral perfusion is associated with increased WMH in persons with HF, but not with the other MRI indices. Cerebral hypoperfusion and subsequent development of WMH is the widely theorized mechanism of cognitive impairment in HF , 9. InteThe current study is limited in several ways. First, the current study consisted of cross-sectional analyses and case-controlled prospective studies are needed to determine whether higher BMI accelerates brain atrophy in HF. In addition, although BMI is practical and widely used it remains a coarse measure of obesity. More precise and detailed assessments of obesity  would provide key insight into the effects of obesity on the brain in HF through its ability to distinguish between bone, fat, and lean tissue. DEXA imaging would also help clarify the regional effects of obesity on cerebral morphometry . Similarly, although TCD is a non-invasive and reliable measure of cerebral blood flow , it is aIn summary, the current study shows that higher BMI is an independent contributor to reduced brain volume in older adults with HF. The mechanisms of this relationship may involve altered cerebral hemodynamics, but are likely complex and involve multiple physiological processes. Prospective studies are needed to confirm the effects of obesity on neuroimaging indices and clarify the etiological underpinnings.