The effect of the COD: N ratio on mainstream deammonification in an integrated fixed-film activated sludge sequencing batch reactor.

For eight months, a sequencing batch reactor (SBR) with integrated fixed-film activated sludge (IFAS) was operated in ambient temperature to study engineering and practical aspects of application of deammonification for mainstream conditions. For biofilm formation, K3 Kaldnes carriers were used, where the anaerobic ammonium oxidation (anammox) process can occur in deep layers of biofilm, while partial nitritation occurs in oxygen-rich outer layers. After the initial running phase of the reactor (Phase 1) to provide time for microorganisms to adapt, the COD: N ratio increased to around 2.6 in Phase 2 through reducing the ammonium concentration and increasing COD in synthetic wastewater to get closer to mainstream conditions. The total reaction time in each half-day batch cycle was kept 625 min throughout various phases, but the duration of intermittent aeration was regulated at 4 ± 1 min. While final nitrogen removal efficiency (NRE) for Phase 1 was 43%, at the end of Phase 2, it decreased to 37%. However, a maximum NRE at 90% was achieved during Phase 2. The identification of the responsible microorganisms was made through Fluorescence in situ hybridization (FISH), while Mixed Liquor Suspended Solid (MLSS) and Mixed Liquor Volatile Suspended Solid (MLVSS) was used to estimate the physical presence of bacteria. Ammonium oxidizing bacteria (AOB) and anaerobic ammonia-oxidizing bacteria (AnAOB) were dominant bacteria, respectively. The adverse effects of a gradual increase of COD: N ratio from 0.17 to more than 2.0 caused a decline in NRE to around 15%.

Theoretical optimal cricothyroidotomy incision length in female subjects, following identification of the cricothyroid membrane by digital palpation.

BACKGROUND: Misidentification of the cricothyroid membrane is frequent in females, placing them at risk of difficult or failed cricothyroidotomy in the event of failed oxygenation. If anatomy is impalpable, the current guidelines of the Difficult Airway Society, based on expert opinion, recommend an 8-10 cm vertical incision to facilitate access to the cricothyroid membrane. At present no evidence-based guideline exists regarding optimum site or length. We investigated the likelihood of inclusion of the cricothyroid membrane, within hypothetical vertical midline incisions, in a female population. METHODS: We asked clinicians to identify the cricothyroid membrane in both the neutral and extended head positions using palpation, the point identified acting as the theoretical midpoint of a cricothyroidotomy incision. We then identified the cricothyroid membrane using ultrasound. We determined the minimum incision length that would be required to ensure that the cricothyroid membrane lay within its boundaries, if clinician digital palpation was the method of cricothyroid membrane localisation. RESULTS: Ninety female subjects were recruited. Theoretical incisions of 7 and 8 cm were required for successful cricothyroidotomy in the neutral and extended head positions respectively. This was necessary because of the high failure rate of cricothyroid membrane identification (80.9%) and the wide range of error (7.2 cm in a vertical plane). CONCLUSIONS: Based on clinical estimation of the location of the cricothyroid membrane, an incision length of 8 cm, using the clinician's best estimate as its midpoint, would overlie all cricothyroid membrane locations. Our data support the current Difficult Airway Society guidelines for cricothyroidotomy incision length.

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems.

New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive "smart" MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.

Evaluation of the effect of intra-operative intravenous fluid on post-operative pain and pulmonary function: a randomized trial comparing 10 and 30 ml kg(-1) of crystalloid.

BACKGROUND: Existing evidence suggests that administration of intravenous fluids has been shown to improve outcomes including pain in gynecological laparoscopic surgery but the optimum fluid dose has not been determined. AIMS: To determine the effect of administration of intravenous fluids on post-operative pain and pulmonary function after gynecological laparoscopy. METHODS: In a prospective randomized double-blinded study 100 ASA 1 and 2 elective patients undergoing gynecological laparoscopy were randomized to receive intravenous compound sodium lactate 10 ml kg(-1) (CSL10-restrictive) or 30 ml kg(-1) (CSL30-liberal) administered intra-operatively. The primary outcome measure was the post-operative pain score at 24, 48 and 72 h, assessed by 0-10 verbal rating scale (VRS). Pulmonary function (FEV1, FVC, PEFR) and oxygen saturation were also measured. RESULTS: Patients who received CSL 30 had lower post-operative pain scores than CSL 10 (ANCOVA-mean difference = 0.47, 95 % CI 0.11-0.83, P = 0.01). Post-operative pain VRS was lower in CSL30 than CSL10 at 48 h (mean difference 0.56, 95 % CI 0.04-1.09, P = 0.036). Patients in CSL30 reported shoulder tip pain less frequently than those in CSL10 (30.4 vs. 43.9 % of assessments, P = 0.03, OR 0.58) but reported wound pain more frequently 39.0 vs. 24.2 %, P = 0.01, OR 2.0). Indices of pulmonary function did not differ between groups at any time. CONCLUSIONS: Liberal compared to restrictive administration of i.v. crystalloid is associated with a clinical modest reduction in pain. Pulmonary dysfunction was not increased with liberal fluid administration.

Anaesthetic outcomes in obese parturients: the effect of assessment in the high-risk clinic.

BACKGROUND: Obese parturients are at high risk of complications during anaesthesia and early use of epidural analgesia in labour has been recommended for obese patients during labour. AIM: To assess the outcome of anaesthesia outpatient consultation for obese parturients. METHODS: We retrospectively compared outcomes of obese patients antenatally and an obese and non-obese control group over a 1-year period. Outcomes included potential airway problems, anaesthetic for caesarean section, use and success of epidural analgesia and cervical dilation at epidural placement. RESULTS: The proportion of obese patients who had predictable intubation difficulty was low (5%). Epidural use analgesia in labour (69 vs 36 vs 66%, P = 0.148) was similar between groups (obese, obese controls and non-obese controls, respectively). Cervical dilation at the time of epidural insertion in the obese group (2.0, 1.0-3.0 cm) was not different from obese controls (3.0, 1.75-5.75 cm). There was no difference in the number of attempts required to site the epidural between groups or the number of patients that required resiting of the epidural catheter. General anaesthesia was not required in any emergency case in this group. CONCLUSION: The outcomes of obese patients attending the anaesthetic clinic were mixed. Not all patients who were to advised have epidurals did so but those who did requested them in early labour and there was no requirement for general anaesthesia during emergency caesarean section and adverse airway events were avoided in this group.

Comparison of transversus abdominis plane block vs spinal morphine for pain relief after Caesarean section.

BACKGROUND: Transversus abdominis plane (TAP) block is an alternative to spinal morphine for analgesia after Caesarean section but there are few data on its comparative efficacy. We compared the analgesic efficacy of the TAP block with and without spinal morphine after Caesarean section in a prospective, randomized, double-blinded placebo-controlled trial. METHODS: Eighty patients were randomized to one of four groups to receive (in addition to spinal anaesthesia) either spinal morphine 100 µg (S(M)) or saline (S(S)) and a postoperative bilateral TAP block with either bupivacaine (T(LA)) 2 mg kg(-1) or saline (T(S)). RESULTS: Pain on movement and early morphine consumption were lowest in groups receiving spinal morphine and was not improved by TAP block. The rank order of median pain scores on movement at 6 h was: S(M)T(LA) (20 mm)

Anaesthetic management of a patient with Liddle's syndrome for emergency caesarean hysterectomy.

We describe the anaesthetic management of a patient with Liddle's syndrome during caesarean section and emergency hysterectomy for placenta accreta associated with significant intrapartum haemorrhage. Liddle's syndrome is a rare autosomal dominant disorder characterised by early onset arterial hypertension and hypokalaemic metabolic alkalosis. Additional issues were the presence of short stature, limb hypertonicity and preeclampsia. Initial management with a low-dose combined spinal-epidural technique was subsequently converted to general anaesthesia due to patient discomfort. The management of Liddle's syndrome in the setting of neuraxial and general anaesthesia in a patient undergoing caesarean section is discussed.

A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy ('polypill') on cardiovascular risk factors.

AIM: Our objective was to investigate the effects and tolerability of fixed-dose combination therapy on blood pressure and LDL in adults without elevated blood pressure or lipid levels. METHODS: This was a double-blind randomised placebo-controlled trial in residents of Kalaleh, Golestan, Iran. Following an 8-week placebo run-in period, 475 participants, aged 50 to 79 years, without cardiovascular disease, hypertension or hyperlipidaemia were randomised to fixed-dose combination therapy with aspirin 81 mg, enalapril 2.5 mg, atorvastatin 20 mg and hydrochlorothiazide 12.5 mg (polypill) or placebo for a period of 12 months. The primary outcomes were changes in LDL-cholesterol, systolic and diastolic blood pressure and adverse reactions. Analysis was by intention-to-treat basis. RESULTS: At baseline, there were differences in systolic blood pressure (6 mmHg). Taking account of baseline differences, at 12 months, polypill was associated with statistically significant reductions in blood pressure (4.5/1.6 mmHg) and LDL-cholesterol (0.46 mmol/l). The study drug was well tolerated, but resulted in the modest reductions in blood pressure and lipid levels. CONCLUSION: The effects of the polypill on blood pressure and lipid levels were less than anticipated, raising questions about the reliability of the reported compliance. There is a case for a fully powered trial of a polypill for the prevention of cardiovascular disease.

The effect of weight reduction on ultrasonographic findings of nonalcoholic Fatty liver.

BACKGROUND Non-alcoholic fatty liver (NAFL) includes a spectrum of diseases ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFL is typically seen in association with obesity, diabetes and hypertriglyceridaemia. In order to seek the role of diet therapy in treatment of NAFL, we compared the ultrasonographic findings of patients with fatty liver disease before and after standard diet therapy. METHODS Twenty-three overweight or obese subjects with incidental fatty liver discovered during ultrasonography were included. Subjects underwent 3 months of diet therapy, and anthropometric data including weight, height, BMI, waist circumference, and hip circumference were measured. Ultrasonographic findings were graded from 0 to 3. Changes in ultrasonographic findings and anthropometric data were studied. RESULTS After three months of dieting, the ultrasonographic grade of all patients decreased by one or two grades. Fifteen patients decreased one grade while 8 others decreased by 2 grades. We observed a significant correlation between the decrease in ultrasonographic grade and the decrease in weight and BMI. CONCLUSION Our study indicates that standard diet therapy could be used as an effective treatment for NAFL patients.

Safety and efficacy of new glyceryl trinitrate suppository formula: first double blind placebo-controlled clinical trial.

PURPOSE: This study was designed to assess the safety and efficacy of 0.2 percent glyceryl trinitrate suppository form in the healing of chronic anal fissure. METHODS: Thirty-four patients with symptomatic chronic anal fissures were assigned to 0.2 percent glyceryl trinitrate suppository (n = 21) or placebo (n = 13) in a double blind design. Patient's symptom scores were registered at first visit. A validated daily chart was given to assess their symptoms on a daily basis. Both groups received psyllium from the beginning of the study. They were assessed at two-week intervals for six weeks. Then, they started a washout period of one month and after that were crossed over for another six weeks. Chi-squared, t-tests, and analysis of variance were used for statistical analysis. RESULTS: Complete healing at six weeks was achieved in 12 of 21 patients (57 percent) in the glyceryl trinitrate group and 5 of 13 patients (38 percent) in the placebo (P < 0.05). The overall healing rates at the end of study were 15 of 21 (71 percent) vs. 11 of 13 (84 percent) in the glyceryl trinitrate and placebo groups, respectively (P > 0.05). CONCLUSIONS: Application of 0.2 percent glyceryl trinitrate suppository form represents a new, promising, and effective treatment for chronic anal fissure.

Bioactive properties of nanostructured porous silicon for enhancing electrode to neuron interfaces.

Many different types of microelectrodes have been developed for use as a direct brain-machine interface (BMI) to chronically recording single-neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only on the order of months. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes, but most likely due to damage to surrounding tissue that results in the formation of non-conductive glial scar. Since the extracellular matrix consists of nanostructured fibrous protein assemblies, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. This porous structure could then act as a drug-delivery reservoir to deliver bioactive agents to aid in the repair or survival of cells around the microelectrode, further reducing the glial scar. We, therefore, investigated the suitability of a nanoporous silicon surface layer to increase the biocompatibility of our thin film ceramic-insulated multisite electrodes. In vitro testing demonstrated increased extension of neurites from PC12 pheochromocytoma cells on porous silicon surfaces compared to smooth silicon surfaces. Moreover, the size of the pores and the pore coverage did not interfere with this bioactive surface property, suggesting that large highly porous nanostructured surfaces can be used for drug delivery. The most porous nanoporous surfaces were then tested in vivo and found to be more biocompatible than smooth surface, producing less glial activation and allowing more neurons to remain close to the device. Collectively, these results support our hypothesis that nanoporous silicon may be an ideal material to improve biocompatibility of chronically implanted microelectrodes. The next step in this work will be to apply these surfaces to active microelectrodes, use them to deliver bioactive agents, and test that they do improve neural recordings.

[A rare case of cannabis arteritis]. / Ein seltener Fall von Cannabis-Arteritis.

A 24-year old woman, heavy cannabis smoker with progressive Raynauld's phenomenon and digital necrosis is presented. Systemic sclerosis and other connective tissue disorders as well as arteriosclerosis and arterial emboli were excluded with appropriate laboratory examinations. Arteriography revealed multiple forearm, palmar and digital occlusions with corkscrew-shaped vessels. Based on these characteristic arteriography and clinical findings, the diagnosis of cannabis-arteritis was finally retained. With careful necrectomy, conservative wound dressings and secondary prostacyclin therapy a complete healing of digital necrosis was observed. There was no recurrence during the 6 month-follow-up. This observation demonstrates that cannabis may represent a possible cofactor in the pathogenesis of arteritis in young smokers. Early recognition is important to avoid irreversible complications such as loss of digits.

Extensor-tendon hypoplasia and multiple pterygia: Escobar syndrome in a 7-year-old boy.

Escobar syndrome is a rare condition with autosomal-recessive inheritance, characterised by multiple pterygia, kyphoscoliosis, multiple joint contractures and craniofacial dysmorphisms. A number of other abnormalities are also attributed to the syndrome. Here, we present a case of isolated extrinsic extensor-tendon hypoplasia of the right index finger in a 7-year-old patient with Escobar syndrome. To our knowledge, this has not been previously described in connection with this syndrome.

Complementary intrastrand base pairing during initiation of Herpes simplex virus type 1 DNA replication.

The herpes simplex virus type 1 origin of DNA replication, oriS, contains three copies of the recognition sequence for the viral initiator protein, origin binding protein (OBP), arranged in two palindromes. The central box I forms a short palindrome with box III and a long palindrome with box II. Single-stranded oriS adopts a conformation, oriS*, that is tightly bound by OBP. Here we demonstrate that OBP binds to a box III-box I hairpin with a 3' single-stranded tail in oriS*. Mutations designed to destabilize the hairpin abolish the binding of OBP to oriS*. The same mutations also inhibit DNA replication. Second site complementary mutations restore binding of OBP to oriS* as well as the ability of mutated oriS to support DNA replication. OriS* is also an efficient activator of the hydrolysis of ATP by OBP. Sequence analyses show that a box III-box I palindrome is an evolutionarily conserved feature of origins of DNA replication from human, equine, bovine, and gallid alpha herpes viruses. We propose that oriS facilitates initiation of DNA synthesis in two steps and that OBP exhibits exquisite specificity for the different conformations oriS adopts at these stages. Our model suggests that distance-dependent cooperative binding of OBP to boxes I and II in duplex DNA is succeeded by specific recognition of a box III-box I hairpin in partially unwound DNA.

Body surface area: Du Bois and Du Bois revisited.

The Du Bois and Du Bois body surface area (BSA) equation is used widely to normalise physiological parameters. However, that only nine subjects were used in its derivation does not appear to be well known and does not justify its ubiquitous application. Furthermore, the derivation appears to be hampered by a lack of modern statistical methods and the omission of a large amount of available data. We have shown that the omitted data, obtained by measurement of the length of body parts, were identical to the data obtained by encasing subjects in moulds ¿BSA (moulds; cm2) = [1.00 (0.02)] x BSA (linear measurements) + [123 (347)]¿. Non-linear regression analysis of the BSA of all 42 subjects reported by Du Bois and Du Bois gave new values for the constants of the model ¿BSA (cm2) = 94.9 x [weight (kg)0.441] x [height (cm)0.655]¿. Although the original equation obtained by Du Bois and Du Bois was found to be adequate in adults, we recommend that it should not be used in daily practice, owing to the low number of subjects used in its derivation. The work presented here has placed the original results of Du Bois and Du Bois on a more robust statistical footing, yielding values for the model constants that would have been obtained if Du Bois and Du Bois had had access to modern statistical methods.

Comparing different methods of assessing body composition in end-stage renal failure.

BACKGROUND: Accurate measurement of nutritional status in patients with end-stage renal disease is important because of its clear association with prognosis. Total body water (TBW) has additionally been recently recognized as an independent prognostic value because of its relationship with hypertension and cardiac morbidity. The current study was designed to assess the utility of surrogate markers of nutritional state and TBW in patients with end-stage renal disease. METHODS: Fifty-four patients with renal disease were studied. TBW obtained using the deuterium dilution technique was compared with estimates derived from anthropometric measures of TBW, including 58% body weight, Watson equations, and bioelectrical impedance analysis (BIA). Anthropometrically derived fat-free mass (FFM) was compared with BIA-derived estimates. Total body nitrogen (TBN) measurements were correlated with TBW estimates and BIA-derived resistance. RESULTS: TBW was significantly underestimated by the Watson equation (mean difference, -1.751 L, P = 0.01) and the 58% body weight approximation significantly overestimated it (mean difference, 1.792 L, P = 0.04). The Kushner BIA estimation of TBW did not significantly differ from that of the gold standard determined from D2O dilution (mean difference, -1.221 L, P = 0.12) and was also the method that showed the best agreement with the D2O estimate. However, the limits of agreement were large. Accurate prediction equations for FFM (FFM = -21.768 + 0.001 x ht2 + 6630.669 x 1/R + 0.312 x wt, R2 = 0.95) and TBN (TBN = -668.324 - 3.963 x age + 10.133 x wt + 0. 045 x ht2 + 32141.457 x 1/R, R2 = 0.91) were derived from BIA obtained resistance. CONCLUSIONS: The estimation of TBW varies significantly depending on the method of calculation. BIA is the most accurate surrogate marker for the measurement of both TBW and other parameters of body composition.

The predictive value of body protein for chemotherapy-induced toxicity.

BACKGROUND: The use of body surface area in determining chemotherapy dosing, particularly in the obese, remains controversial. Total body nitrogen (TBN) measurement in patients with serious illness has been suggested to be an accurate predictor of clinical course. The ability of TBN to predict chemotherapy-induced neutropenia was examined in the current study. METHODS: TBN measurements were performed in 31 female outpatients with breast carcinoma who were undergoing standard cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based chemotherapy (median age, 48 years; range, 26- 77 years). TBN was measured using the in vivo neutron capture analysis technique on Day 1 of Cycles 2-6. The chemotherapy toxicity index used was the absolute neutrophil count nadir (ANCN). Neutropenia was defined as an ANCN < 1.0 x 10(9)/L. The nitrogen index (NI) (TBN expressed as a percentage of age-, gender-. and height-matched healthy patients) then was compared with the corresponding ANCN values. RESULTS: Using receiver operating characteristics analysis, a "cut-off" value of NI = 0.89 was found. In this group of patients, when the NI was < 0.89, 11 of 13 courses in 7 patients (85%) led to an ANCN of < 1.0 x 10(9)/L, and when the NI was > 0.89, 29 of 109 courses (27%) led to an ANCN of < 1.0 x 10(9)/L (P < 0.0001). CONCLUSIONS: In this small group of breast carcinoma patients, the NI was found to be the most powerful predictor of neutropenia after CMF-based chemotherapy. The authors conclude that NI may be a useful clinical tool in identifying patients at a higher risk of chemotherapy-induced toxicity when widely distributed drug combinations such as CMF are used, and warrants further study with other commonly used drugs or drug regimens.

A novel conformation of the herpes simplex virus origin of DNA replication recognized by the origin binding protein.

The Herpes simplex virus type I origin binding protein (OBP) is a sequence-specific DNA-binding protein and a dimeric DNA helicase encoded by the UL9 gene. It is required for the activation of the viral origin of DNA replication oriS. Here we demonstrate that the linear double-stranded form of oriS can be converted by heat treatment to a stable novel conformation referred to as oriS*. Studies using S1 nuclease suggest that oriS* consists of a central hairpin with an AT-rich sequence in the loop. Single-stranded oligonucleotides corresponding to the upper strand of oriS can adopt the same structure. OBP forms a stable complex with oriS*. We have identified structural features of oriS* recognized by OBP. The central oriS palindrome as well as sequences at the 5' side of the oriS palindrome were required for complex formation. Importantly, we found that mutations that have been shown to reduce oriS-dependent DNA replication also reduce the formation of the OBP-oriS* complex. We suggest that oriS* serves as an intermediate in the initiation of DNA replication providing the initiator protein with structural information for a selective and efficient assembly of the viral replication machinery.