Aim: To analyse the outcome of high volume cataract surgery in a developing country, community based, high volume eye hospital.
Methods: In a non-comparative interventional case series, the authors reviewed the surgical outcomes of 593 patients with cataract operated upon by three high volume surgeons on six randomly selected days. There were 318 female (54%) and 275 male (46%) patients. Their mean age was 59.57 (SD 10.13) years. The majority of the patients underwent manual small incision cataract surgery (manual SICS). Extracapsular cataract extraction with posterior chamber intraocular lens (ECCE-PCIOL) and intracapsular cataract extraction (ICCE) were also done on a few patients as clinically indicated.
Results: Best corrected visual acuity of ⩾6/18 was achieved in 94% of the 520 patients who could be followed up on the 40th postoperative day (88% follow up rate). Intraoperative and immediate postoperative complications as defined by OCTET occurred in 11 (1.9%) and 75 (12.6%) patients, respectively. Average surgical time of 3.75 minutes per case (16–18 cases per hour) was achieved. Statistically significant risk factors for outcomes were found to be age >60, sex, and surgeon.
Conclusion: High volume surgery using appropriate techniques and standardised protocols does not compromise quality of outcomes.
cataract surgery; developing country
It was a zoological sensation when a living specimen of the coelacanth was first discovered in 1938, as this lineage of lobe-finned fish was thought to have gone extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features . Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain, and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues demonstrate the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
Diabetes increases the risk of adverse cardiac outcomes and is considered a coronary artery disease (CAD) equivalent. We examined whether coronary vascular dysfunction, an early manifestation of CAD, accounts for increased risk among patients with diabetes compared to non-diabetics.
Methods and Results
2783 consecutive patients (1172 diabetics and 1611 non-diabetics) underwent quantification of coronary flow reserve (CFR=stress divided by rest myocardial blood flow) by PET and were followed for a median of 1.4 years (Q1–Q3: 0.7–3.2). The primary endpoint was cardiac death. Impaired CFR (below the median) was associated with an adjusted 3.2 and 4.9-fold increase in the rate of cardiac death for diabetics and non-diabetics, respectively (p=0.0004). Addition of CFR to clinical and imaging risk models improved risk discrimination both diabetics and non-diabetics (c-index: 0.77 to 0.79, p=0.04, and 0.82 to 0.85, p=0.03, respectively). Diabetic patients without known CAD with impaired CFR experienced a rate of cardiac death comparable to that for non-diabetic patients with known CAD (2.8 vs 2.0%/year, P=0.33). Conversely, diabetics without known CAD and preserved CFR had very low annualized cardiac mortality, which was similar to patients without known CAD or diabetes and normal stress perfusion and systolic function (0.3 vs. 0.5%/year, P=0.65).
Coronary vasodilator dysfunction is a powerful, independent correlate of cardiac mortality among both diabetics and non-diabetics and provides meaningful incremental risk stratification. Among diabetic patients without CAD, those with impaired CFR have event rates comparable to patients with prior CAD while those with preserved CFR have event rates comparable to non-diabetics.
coronary disease; diabetes mellitus; imaging; myocardial perfusion imaging
The yersiniae (Enterobacteriaceae) occupy a variety of niches, including some in human and flea hosts. Metabolic adaptations of the yersiniae, which contribute to their success in these specialized environments, remain largely unknown. We report results of an investigation of the transcriptome under aerobic and anaerobic conditions for Y. intermedia, a non-pathogenic member of the genus that has been used as a research surrogate for Y. pestis. Y. intermedia shares characteristics of pathogenic yersiniae, but is not known to cause disease in humans. Oxygen restriction is an important environmental stimulus experienced by many bacteria during their life-cycles and greatly influences their survival in specific environments. How oxygen availability affects physiology in the yersiniae is of importance in their life cycles but has not been extensively characterized.
Tiled oligonucleotide arrays based on a draft genome sequence of Y. intermedia were used in transcript profiling experiments to identify genes that change expression in response to oxygen availability during growth in minimal media with glucose. The expression of more than 400 genes, constituting about 10% of the genome, was significantly altered due to oxygen-limitation in early log phase under these conditions. Broad functional categorization indicated that, in addition to genes involved in central metabolism, genes involved in adaptation to stress and genes likely involved with host interactions were affected by oxygen-availability. Notable among these, were genes encoding functions for motility, chemotaxis and biosynthesis of cobalamin, which were up-regulated and those for iron/heme utilization, methionine metabolism and urease, which were down-regulated.
This is the first transcriptome analysis of a non-pathogenic Yersinia
spp. and one of few elucidating the global response to oxygen limitation for any of the yersiniae. Thus this study lays the foundation for further experimental characterization of oxygen-responsive genes and pathways in this ecologically diverse genus.
To evaluate whether impaired vasodilator function, an early manifestation of coronary artery disease which precedes angiographic stenosis, accounts for increased risk among patients with moderate to severe renal dysfunction.
Patients with renal dysfunction are at increased risk of adverse cardiac outcomes, even in the absence of overt myocardial ischemia or infarction.
We included 866 consecutive patients with moderate to severe renal dysfunction referred for rest and stress myocardial perfusion PET and followed them for a median of 1.28 years (inter-quartile range: 0.64–2.34). Regional myocardial perfusion abnormalities were assessed by semiquantitative visual analysis of PET images. Rest and stress myocardial blood flow (MBF) were calculated using factor analysis and a 2-compartment kinetic model, and were used to compute coronary flow reserve (stress/rest MBF). The primary endpoint was cardiac death.
Overall 3-year cardiac mortality was 16.2%. After adjusting for clinical risk, left ventricular ejection fraction, as well as the magnitude of scar and/or ischemia, coronary flow reserve below the median (<1.5) was associated with a 2.1-fold increase in the risk of cardiac death (95%CI 1.3–3.5, P= 0.004). Incorporation of coronary flow reserve into cardiac death risk assessment models resulted in an increase in the c-index from 0.75 to 0.77 (P=0.05) and in a net reclassification improvement (NRI) of 0.142 (95%CI 0.076–0.219). Among patients at intermediate risk based on all data other than coronary flow reserve, the NRI was 0.489 (95%CI 0.192–0.836). Corresponding improvements in risk assessment for mortality from any cause were also demonstrated.
The presence of coronary vascular dysfunction in patients with moderate to severe renal dysfunction, as assessed by PET, is a powerful, independent predictor of cardiac mortality and provides meaningful incremental risk stratification over conventional markers of clinical risk.
coronary artery disease; chronic kidney disease; blood flow; imaging; atherosclerosis; ischemia
Signal transducer and activator of transcription 3 (STAT3) is a key mediator of the inflammatory response by macrophages and other immune cell types. The naturally occurring polyphenol resveratrol is associated with anti-proliferative and anti-inflammatory properties via mechanisms implicating inhibition of STAT3 signaling. Here, we report that the small-molecule analogs of resveratrol, RSVA314 and RSVA405, are potent inhibitors of STAT3. RSVA314 and RSVA405 inhibited both constitutive and stimulated STAT3 in HEK293 cells and lipopolysaccharide (LPS)-activated RAW 264.7 macrophages, respectively. The small-molecule analogs inhibited STAT3 nearly 50 times more potently than did resveratrol (apparent IC50 ~ 0.5 μM). We further show that RSVA405 interfered with the inflammatory response by RAW 264.7 cells upon LPS stimulation by inhibiting IKK and IκBα phosphorylation and by decreasing the expression of several cytokines, including the NF-κB target genes, tumor necrosis factor-α and interleukin-6. Downstream activation of STAT1 upon LPS stimulation was also inhibited by RSVA405. Consequently, RSVA405 significantly interfered with the phagocytotic activity and proliferation of LPS-activated RAW 264.7 macrophages. Finally, we found that the effect of the two small-molecule analogs on STAT3 phosphorylation could be prevented by inhibitors of protein tyrosine phosphatases (PTPs), indicating that the small-molecules acted by promoting the dephosphorylation of STAT3 by PTPs.
STAT3; Inflammation; RSVA314; RSVA405; Resveratrol
The National Quality Forum (NQF) has endorsed a performance measure designed to increase imaging efficiency for the evaluation of pulmonary embolism (PE) in the emergency department (ED). To our knowledge, no published data have examined the effect of patient-level predictors on performance.
To quantify the prevalence of avoidable imaging in ED patients with suspected PE, we performed a prospective, multicenter observational study of ED patients evaluated for PE from 2004 through 2007 at 11 US EDs. Adult patients tested for PE were enrolled, with data collected in a standardized instrument. The primary outcome was the proportion of imaging that was potentially avoidable according to the NQF measure. Avoidable imaging was defined as imaging in a patient with low pretest probability for PE, who either did not have a D-dimer test ordered or who had a negative D-dimer test result. We performed subanalyses testing alternative pretest probability cutoffs and imaging definitions on measure performance as well as a secondary analysis to identify factors associated with inappropriate imaging. χ2 Test was used for bivariate analysis of categorical variables and multivariable logistic regression for the secondary analysis.
We enrolled 5940 patients, of whom 4113 (69%) had low pretest probability of PE. Imaging was performed in 2238 low-risk patients (38%), of whom 811 had no D-dimer testing, and 394 had negative D-dimer test results. Imaging was avoidable, according to the NQF measure, in 1205 patients (32%; 95% CI, 31%-34%). Avoidable imaging owing to not ordering a D-dimer test was associated with age (odds ratio [OR], 1.15 per decade; 95% CI, 1.10-1.21). Avoidable imaging owing to imaging after a negative D-dimer test result was associated with inactive malignant disease (OR, 1.66; 95% CI, 1.11-2.49).
One-third of imaging performed for suspected PE may be categorized as avoidable. Improving adherence to established diagnostic protocols is likely to result in significantly fewer patients receiving unnecessary irradiation and substantial savings.
B-type natriuretic peptide (BNP) is used widely to exclude heart failure (HF) in patients with dyspnea. However, most studies of BNP have focused on diagnosing HF with reduced ejection fraction (EF). We hypothesized that a normal BNP (≤ 100 pg/ml) is relatively common in HF with preserved EF (HFpEF), a heterogeneous disorder commonly associated with obesity. We prospectively studied 159 consecutive patients enrolled in the Northwestern University HFpEF Program. All subjects had symptomatic HF with EF>50% and elevated pulmonary capillary wedge pressure (PCWP). BNP was tested at baseline in all subjects. We compared clinical characteristics, echocardiographic parameters, invasive hemodynamics, and outcomes among HFpEF patients with normal (≤ 100 pg/ml) vs. elevated (>100 pg/ml) BNP. Of the 159 HFpEF patients, 46 (29%) had BNP ≤ 100 pg/ml. Subjects with normal BNP were younger, more often female, had higher rates of obesity and higher body-mass index, and less commonly had chronic kidney disease and atrial fibrillation. Both EF and PCWP were similar in normal vs. elevated BNP groups (62±7 vs. 61±7% [P=0.67] and 25±8 vs. 27±9 mmHg [P=0.42], respectively). Elevated BNP was associated with enlarged left atrial volume, worse diastolic function, abnormal right ventricular structure/function, and worse outcomes (e.g., adjusted hazard ratio for HF hospitalization = 4.0, 95% confidence interval 1.6-9.7, P=0.003). In conclusion, a normal BNP is present in 29% of symptomatic outpatients with HFpEF who have elevated PCWP, obesity is likely the primary driver of this finding, and although BNP is useful as a prognostic marker in HFpEF, a normal BNP does not exclude the outpatient diagnosis of HFpEF.
B-type natriuretic peptide; diastolic heart failure; obesity; hemodynamics; echocardiography; outcomes
Epidemiological studies have argued that green tea could mitigate diabetes and its complications. This study investigated the phytophenolic profile of Mauritian green tea and its antioxidant propensity. The effect of green tea on the risk factors: waist-hip ratio, glucose level, arterial pressure, antioxidant status, and alanine aminotransferase (ALT) in prediabetics was assessed. The experimental group consumed 3 cups of green tea daily for 14 weeks followed by a 2-week washout period. The control group followed a water regimen. Green tea contained high level of phenolics related to its antioxidant power. Green tea suppressed waist-hip ratio of women from a significant increase and suppressed mean arterial pressure of men and women from a significant decrease after week 14. It reduced ALT level in women by 13.0% (P < 0.1) while increasing the antioxidant potential of men and women sera by 2.7% (P < 0.1) and 5.1% (P < 0.1). The study timescale may have been too short to enable demonstration of effects on fasting plasma glucose and HbA1c outcomes. Green tea regimen could form part of a healthy lifestyle that might ameliorate features of metabolic syndrome and subsequent risks for diabetes and its complications. This trial is registered with ClinicalTrials.gov NCT01248143.
To compare topical natamycin vs voriconazole in the treatment of filamentous fungal keratitis.
This phase 3, double-masked, multicenter trial was designed to randomize 368 patients to voriconazole (1%) or natamycin (5%), applied topically every hour while awake until reepithelialization, then 4 times daily for at least 3 weeks. Eligibility included smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400.
Main Outcome Measures
The primary outcome was best spectacle-corrected visual acuity at 3 months; secondary outcomes included corneal perforation and/or therapeutic penetrating keratoplasty.
A total of 940 patients were screened and 323 were enrolled. Causative organisms included Fusarium (128 patients [40%]), Aspergillus (54 patients [17%]), and other filamentous fungi (141 patients [43%]). Natamycin-treated cases had significantly better 3-month best spectacle-corrected visual acuity than voriconazole-treated cases (regression coefficient=−0.18 logMAR; 95% CI, −0.30 to −0.05; P=.006). Natamycin-treated cases were less likely to have perforation or require therapeutic penetrating keratoplasty (odds ratio=0.42; 95% CI, 0.22 to 0.80; P=.009). Fusarium cases fared better with natamycin than with voriconazole (regression coefficient=−0.41 logMAR; 95% CI, −0.61 to −0.20; P<.001; odds ratio for perforation=0.06; 95% CI, 0.01 to 0.28; P<.001), while non-Fusarium cases fared similarly (regression coefficient=−0.02 logMAR; 95% CI, −0.17 to 0.13; P=.81; odds ratio for perforation=1.08; 95% CI, 0.48 to 2.43; P=.86).
Natamycin treatment was associated with significantly better clinical and microbiological outcomes than voriconazole treatment for smear-positive filamentous fungal keratitis, with much of the difference attributable to improved results in Fusarium cases.
Application to Clinical Practice
Voriconazole should not be used as monotherapy in filamentous keratitis.
clinicaltrials.gov Identifier: NCT00996736
The hunt for alternative sources of energy generation that are inexpensive, ecofriendly, renewable and can replace fossil fuels is on, owing to the increasing demands of energy. One approach in this direction is the conversion of plant residues into biofuels wherein lignocellulose, which forms the structural framework of plants consisting of cellulose, hemicellulose and lignin, is first broken down and hydrolyzed into simple fermentable sugars, which upon fermentation form biofuels such as ethanol. A major bottleneck is to disarray lignin which is present as a protective covering and makes cellulose and hemicellulose recalcitrant to enzymatic hydrolysis. A number of biomass deconstruction or pretreatment processes (physical, chemical and biological) have been used to break the structural framework of plants and depolymerize lignin. This review surveys and discusses some major pretreatment processes pertaining to the pretreatment of plant biomass, which are used for the production of biofuels and other value added products. The emphasis is given on processes that provide maximum amount of sugars, which are subsequently used for the production of biofuels.
Pretreatment; Biomass; Lignin; Cellulose; Biofuel
To analyse predictors of clinical outcome in fungal keratitis.
Data was collected during a prospective, randomized, controlled, double-masked clinical trial of treatment for fungal keratitis. Clinical features at presentation and demographics were collected at the enrolment visit for all patients. Pre-specified clinical outcomes included 3-month visual acuity and infiltrate/scar size, time to re-epithelialization, and corneal perforation. A separate multivariable model with each outcome as the dependent variable included all predictor variables.
Predictors for worse 3-month visual acuity include older age (P=0.024), worse presentation visual acuity (P<0.001), larger infiltrate size at presentation (P<0.001), and pigmented ulcer (P=0.030). Larger infiltrate size at presentation was a significant predictor of worse 3-month infiltrate/scar size (P<0.001). Larger epithelial defect size was a significant predictor of perforation (P=0.0013). Predictors of longer time to re-epithelialization include infiltrate size at presentation (P<0.001) and older age (P=0.025).
Ulcer severity at presentation is highly predictive of worse outcomes. Presentation of clinical characteristics such as baseline acuity and infiltrate scar can provide important information to clinicians about prognosis, and may help guide management and treatment decisions. Prevention of corneal ulcer remains important, as it is difficult to change the course of the ulcer once it has begun.
fungus; keratitis; risk factors
Gorham's disease is a rare disorder characterized by clinical and radiological disappearance of bone by proliferation of non-neoplastic vascular tissue. The disease was first reported by Jackson in 1838 in a boneless arm. The disease was then described in detail in 1955 by Gorham and Stout. Since then, about 200 cases have been reported in the literature, with only about 28 cases involving the spine. We report 2 cases of Gorham's disease involving the spine and review related literature to gain more understanding about this rare disease.
Gorham's disease; Spine
Ceftriaxone is a commonly used antibiotic in children for various infections like respiratory tract infection, urinary tract infection and enteric fever. Hypersensitive reactions following ceftriaxone therapy are uncommon but are potentially life-threatening. The rash can resemble viral exanthems and may lead to a delay in the recognition and prompt treatment. Here we report a 7-year-old boy who presented with fever and rash with emphasis on recognizing ceftriaxone hypersensitivity and its management.
Ceftriaxone allergy; child; hypersensitivity; maculopapular rash
There is an urgent need for novel polymeric carriers that can selectively deliver a large dose of chemotherapeutic agents into hepatic cancer cells to achieve high therapeutic activity with minimal systemic side effects. PAMAM dendrimers are characterized by a unique branching architecture and a large number of chemical surface groups suitable for coupling of chemotherapeutic agents. In this article, we report the coupling of N-acetylgalactosamine (NAcGal) to generation 5 (G5) of poly(amidoamine) (PAMAM-NH2) dendrimers via peptide and thiourea linkages to prepare NAcGal-targeted carriers used for targeted delivery of chemotherapeutic agents into hepatic cancer cells. We describe the uptake of NAcGal-targeted and non-targeted G5 dendrimers into hepatic cancer cells (HepG2) as a function of G5 concentration and incubation time. We examine the contribution of the asialoglycoprotein receptor (ASGPR) to the internalization of NAcGal-targeted dendrimers into hepatic cancer cells through a competitive inhibition assay. Our results show that uptake of NAcGal-targeted G5 dendrimers into hepatic cancer cells occurs via ASGPR-mediated endocytosis. Internalization of these targeted carriers increased with the increase in G5 concentration and incubation time following Michaelis–Menten kinetics characteristic of receptor-mediated endocytosis. These results collectively indicate that G5-NAcGal conjugates function as targeted carriers for selective delivery of chemotherapeutic agents into hepatic cancer cells.
Nanoparticle; Dendrimers; Drug delivery; Flow cytometry; Hepatocyte
A prospective, randomised study was carried out to compare the effect of pre-operative shaving with chemical depilation on wound infection in 100 patients. It was shown that depilatory creams saved time for pre-operative preparation and had an advantage in areas where shaving was difficult. The use of depilatory creams was shown to be effective, atraumatic, non-toxic and could be self-administered. Depilatory creams could be used safely on granulating wounds and did not give rise to bacterial growth. Their use was associated with a significant reduction in skin-surface bacteria and was cheaper compared with shaving. The best practice is to refrain from hair removal unless it interferes with the surgical procedure or wound closure. If hair has to be removed, it should be done using a depilatory cream. The depilatory cream has an advantage in areas which are difficult to shave or if the patient is scheduled to undergo diagnostic procedures and operations in the same area in close succession. The fight against post-operative wound infections has long been undertaken by practitioners. The authors realise that surgical-site infections are frequently caused by the bacteria commonly found on the skin; hence, reducing the number of bacteria on the skin has been a common pre-operative practice.
Preparation; Shave; Cream
The Bardet-Biedl syndrome (BBS), a rare autosomal recessive disorder, was first described by Bardet and Biedl in 1920. Here, we are reporting a case of the Bardet-Biedl syndrome with hypokalaemic paralysis.
A 22 years old male patient presented with an acute onset, rapidly progressive, flaccid weakness in all four limbs. An examination revealed a moon shaped face, acanthosis nigricans, lower limb polydactyly, central obesity, small testicular size, absence of the axillary and pubic hairs, severely impaired social adaptive functioning and retinitis pigmentosa. The central nervous system examination showed hypotonia, a grade zero power and absent reflexes. The laboratory reports showed that the patient had hypokalaemia and diabetes mellitus.
The literature showed hypokalaemic paralysis as a rare complication of the Bardet-Biedl syndrome.
Bardet-Biedl syndrome; Hypokalaemic paralysis; Obesity; Retinitis pigmentosa; Ciliopathies; Autosomal recessive disorder
Background: Iron is vital for all the living organisms. However, excess iron is hazardous because it produces free radical formation. Therefore, the iron absorption is carefully regulated to maintain an equilibrium between the absorption and the body loss of iron. Considering the lack of specific excretory pathways for iron in humans, an iron overload in the tissues is frequently encountered. It can be precipitated by a variety of conditions such as increased iron absorption, as is seen in haemochromatosis or a frequent parenteral iron administration, as is seen in thalassaemia and sickle cell anaemia patients (a transfusional overload).
Objectives: To demonstrate the iron overload at an early stage by oral exfoliative cytology in the oral mucosal cells of thalassaemia and sickle cell anaemia patients and to compare the presence of iron in the exfoliated oral epithelial cells with that of the serum ferritin levels in those patients.
Materials and Methods: The present study comprised of 40 β– thalassaemia major and 20 sickle cell anaemia patients who were undergoing repeated blood transfusions of a minimum of 15/more, along with 60 clinically healthy individuals. Scrapings were obtained from the buccal mucosa and they were smeared onto glass slides. Then the slides were stained with a Perl’s Prussian staining kit and they were examined under a light microscope.
Results: 72.5% of the thalassaemia patients and 35% of the sickle cell anaemia patients revealed a positivity for the Perl’s Prussian blue reaction and none of the controls showed this positivity. It was also observed that as the serum ferritin levels increased, the iron overload in the oral mucosal cells of the thalassaemia patients also increased, which was not statistically significant, whereas it was statistically significant in case of the sickle cell anemia patients.
Conclusion: Since the exfoliative cytology is a simple, painless, non-invasive and a quick procedure to perform, a lot of research should be carried out on the correlation of the Perl’s Prussian blue reaction to the serum ferritin levels.
Iron; Thalassaemia; Sickle cell anaemia; Perl’s Prussian blue reaction
Excessive heat exposure reduces intestinal integrity and post-absorptive energetics that can inhibit wellbeing and be fatal. Therefore, our objectives were to examine how acute heat stress (HS) alters intestinal integrity and metabolism in growing pigs. Animals were exposed to either thermal neutral (TN, 21°C; 35–50% humidity; n = 8) or HS conditions (35°C; 24–43% humidity; n = 8) for 24 h. Compared to TN, rectal temperatures in HS pigs increased by 1.6°C and respiration rates by 2-fold (P<0.05). As expected, HS decreased feed intake by 53% (P<0.05) and body weight (P<0.05) compared to TN pigs. Ileum heat shock protein 70 expression increased (P<0.05), while intestinal integrity was compromised in the HS pigs (ileum and colon TER decreased; P<0.05). Furthermore, HS increased serum endotoxin concentrations (P = 0.05). Intestinal permeability was accompanied by an increase in protein expression of myosin light chain kinase (P<0.05) and casein kinase II-α (P = 0.06). Protein expression of tight junction (TJ) proteins in the ileum revealed claudin 3 and occludin expression to be increased overall due to HS (P<0.05), while there were no differences in claudin 1 expression. Intestinal glucose transport and blood glucose were elevated due to HS (P<0.05). This was supported by increased ileum Na+/K+ ATPase activity in HS pigs. SGLT-1 protein expression was unaltered; however, HS increased ileal GLUT-2 protein expression (P = 0.06). Altogether, these data indicate that HS reduce intestinal integrity and increase intestinal stress and glucose transport.
Cerebrospinal fluid (CSF) collection in the eyelid is known as blepharocele. It is rarely reported in adults. In this report, we describe one such patient who developed a non-resolving swelling of the left upper eyelid associated with mechanical ptosis following a head injury. He had fractures involving the left orbital rim and roof, and the medial and lateral walls. His left frontal sinus was hypoplastic. The diagnosis of CSF blepharocele was made based on clinical, biochemical and radiological findings. He underwent transcranial repair of the left frontobasal dural tear with a good recovery.
Cerebrospinal Fluid; Eyelid; Basilar Skull Fracture; Case Report; India
Simultaneous saccharification and co-fermentation (SSCF) process involves enzymatic hydrolysis of pretreated lignocellulosic biomass and fermentation of glucose and xylose in one bioreactor. The optimal temperatures for enzymatic hydrolysis are higher than the standard fermentation temperature of ethanologenic Saccharomyces cerevisiae. Moreover, degradation products resulting from biomass pretreatment impair fermentation of sugars, especially xylose, and can synergize with high temperature stress. One approach to resolve both concerns is to utilize a strain background with innate tolerance to both elevated temperatures and degradation products.
In this study, we screened a panel of 108 wild and domesticated Saccharomyces cerevisiae strains isolated from a wide range of environmental niches. One wild strain was selected based on its growth tolerance to simultaneous elevated temperature and AFEX™ (Ammonia Fiber Expansion) degradation products. After engineering the strain with two copies of the Scheffersomyces stipitis xylose reductase, xylitol dehydrogenase and xylulokinase genes, we compared the ability of this engineered strain to the benchmark 424A(LNH-ST) strain in ethanol production and xylose fermentation in standard lab medium and AFEX pretreated corn stover (ACS) hydrolysates, as well as in SSCF of ACS at different temperatures. In SSCF of 9% (w/w) glucan loading ACS at 35°C, the engineered strain showed higher cell viabilities and produced a similar amount of ethanol (51.3 g/L) compared to the benchmark 424A(LNH-ST) strain.
These results validate our approach in the selection of wild Saccharomyces cerevisiae strains with thermo-tolerance and degradation products tolerance properties for lignocellulosic biofuel production. The wild and domesticated yeast strains phenotyped in this work are publically available for others to use as genetic backgrounds for fermentation of their pretreated biomass at elevated temperatures.
Thermo-tolerance; Xylose fermentation; S. cerevisiae; SSCF; AFEX; Degradation products; Ethanol
Tetherin, an interferon-inducible membrane protein, inhibits the release of nascent enveloped viral particles from the surface of infected cells. However, the mechanisms underlying virion retention have not yet been fully delineated. Here, we employ biochemical assays and engineered tetherin proteins to demonstrate conclusively that virion tethers are composed of the tetherin protein itself, and to elucidate the configuration and topology that tetherin adopts during virion entrapment. We demonstrate that tetherin dimers adopt an “axial” configuration, in which pairs of transmembrane domains or pairs of glycosylphosphatidyl inositol anchors are inserted into assembling virion particles, while the remaining pair of membrane anchors remains embedded in the infected cell membrane. We use quantitative western blotting to determine that a few dozen tetherin dimers are used to tether each virion particle, and that there is ∼3- to 5-fold preference for the insertion of glycosylphosphatidyl inositol anchors rather than transmembrane domains into tethered virions. Cumulatively, these results demonstrate that axially configured tetherin homodimers are directly responsible for trapping virions at the cell surface. We suggest that insertion of glycosylphosphatidyl inositol anchors may be preferred so that effector functions that require exposure of the tetherin N-terminus to the cytoplasm of infected cells are retained.
The cellular restriction factor, tetherin, prevents HIV-1 and other enveloped virus particles from being disseminated into the extracellular milieu by infiltrating their envelopes and by physically crosslinking them to the cell surface. It is known that tetherin consists of pairs of membrane anchors, situated at either end of a rod-shaped molecule, but how tetherin causes virion tethering has been difficult to unambiguously determine. In this work, we develop genetic and biochemical approaches to probe tetherin molecules that have infiltrated tethered virions. We show that tetherin adopts an “axial” configuration in its functional state, with a pair of membrane anchors situated at one end of the rod-like structure inserted into a tethered virion. While either end of the rod can be inserted into a virion, there is a preference for the insertion of its lipid (glycosylphosphatidyl inositol) modified carboxyl-terminus into virion envelopes. These studies demonstrate unequivocally that the tetherin molecule itself is directly responsible for trapping virions, and dissect the molecular mechanism underpinning its antiviral activity.
Zanthoxylum zanthoxyloides and Z. leprieurii fruits are commonly used in traditional system of medicine for diarrhea, pain, wound healing, etc. in Cameroon, Africa. Z. leprieurii fruits have been chemically studied for its bioactive compounds whereas the investigation on Z. zanthoxyloides fruits is lacking.
After a detailed chemical analysis of the fruits of Z. leprieurii and Z. zanthoxyloides, a series of new acridone alkaloids, namely, 3-hydroxy-1,5,6-trimethoxy-9-acridone (1), 1,6-dihydroxy-3-methoxy-9-acridone (2), 3,4,5,7-tetrahydroxy-1-methoxy-10-methyl-9-acridone (3), 4-methoxyzanthacridone (8), 4-hydroxyzanthacridone (9), 4-hydroxyzanthacridone oxide (2,4’) (10) have been isolated. The known acridones which have been characterized are, helebelicine A (4), 1-hydroxy-3-methoxy-10-methyl-9-acridone (5), 1,3-dihydroxy-4-methoxy-10-methyl-9-acridone (6) and tegerrardin A (7). The in vitro antibacterial and cytotoxic screening of these acridones reveal that compound 3 has a moderate antibacterial activity (MIC 125 μg/mL) against Micrococcus luteus and Pseudomonas aeruginosa while compound 1 shows a moderate cytotoxic effect (IC50 of 86 μM) against WRL-68 (liver cancer cell line). Furthermore, the molecular modeling of these acridones predicted the structural basis for their mode of action and binding affinity for aromatase, quinone reductase and WAAG, a glycosyltransferase involved in bacterial lipopolysaccharide synthesis. Computational approaches, quantitative SAR and modeling studies predicted that acridones 1, 2, 3, 4, 9 and 10 were the inhibitors of glycosyltransferase while 1, 8, 9 and 10, the inhibitors of aromatase.
A total of 10 acridones have been isolated out of which 6 are new (1, 2, 3, 8, 9 and 10). Alkaloids 8, 9 and 10, having novel tetracyclic acridone structure with new carbon skeleton, have now been named as zanthacridone. The quantitative SAR and molecular modeling studies suggested that the compounds 1, 9 and 10 are inhibitors of both aromatase and glycosyltransferase.
Rutaceae; Zanthoxylum zanthoxyloides; Z. leprieurii; Zanthacridones; Structure elucidation; Antibacterial; Cytotoxic activities; Molecular modeling; QSAR studies
Myocardial fat accumulation could occur in diseased hearts. The degree of heterogeneity is unknown because accurate assessment is difficult using conventional 1H-MRS techniques in a beating heart. The purpose of this study was to characterize the distribution of intramyocellular lipid content and to determine its association with disease characteristics. 1H-MRS was performed on formalin-fixed slices of human hearts at various circumferential locations (N=55). 29% of the hearts had the highest fat content measured in the septum, followed by posterior (27%), lateral (26%), and anterior (18%) wall. Age was significantly correlated with the mean fat percentages (r2=0.12, p=0.007). Those who died from cardiovascular disease demonstrated significantly higher and more heterogeneous fat distribution than those who did not (1.62±1.1% vs 0.59±0.4%, p=0.002). In summary, septal fat content is representative of mean fat percentage. Fat content increases with age; fat distribution may be heterogeneous when associated with cardiovascular disease.
cardiac steatosis; magnetic resonance spectroscopy; heterogeneity; ex-vivo