Recent advances in three-dimensional ultrasound virtual cystoscopy in modeling and local staging for urothelial carcinoma with histopathological correlation: a cohort prospective study.

Background: Bladder urothelial carcinoma is an alarming urologic malignancy. Complex factors like modelling and local staging can affect treatment strategy. However, local staging, particularly the muscle invasion status, significantly influences decisions regarding treatment strategies. Therefore, this study aims to evaluate the novel advances of three-dimensional (3D) ultrasound (US) imaging to assess local staging in comparison with conventional cystoscopy. Methods: Forty-three patients with painless haematuria and conventional cystoscopy findings of bladder mass underwent 3D US virtual cystoscopy. All specimens from conventional cystoscopy were processed histologically. Results: Out of 43 participants, 18 (41.9%) patients proved to have invasive urothelial carcinoma by histopathology. The 3D US had a sensitivity of 97.5% and a specificity of 100%; however conventional cystoscopy was accurate in only 53.5% of the studied cases. Furthermore, in the case of malignant ulcers, mural extension into both the submucosal and the muscle layers was more readily appreciated in multiplanar images. Conclusion: 3D US updates are promising for use in bladder tumour modelling and local staging; however, they can be of value in evaluating mural and extramural tumour extent and have proven accuracy.

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma.

INTRODUCTION: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. METHODS: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. RESULTS AND CONCLUSION: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers' expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

Prevalence and Haplotypes of Toxoplasma gondii in Native Village Chickens and Pigs in Peninsular Malaysia.

Toxoplasma gondii is an important zoonotic foodborne parasite capable of infecting almost all warm-blooded animal species worldwide. Toxoplasmosis is usually acquired via ingestion of undercooked infected animal tissues resulting in life-threatening consequences for unborn foetus and immunocompromised individuals. A cross-sectional study was carried out to determine the prevalence of T. gondii infection, its associated risk factors in farms, and haplotypes isolated from the native village chicken and pig populations in Peninsular Malaysia. The seroprevalence of T. gondii in village chickens at the animal level was low at 7.6% (95% CI: 4.60-11.60), while at the farm level, it was 52.0% (95% CI: 31.30-72.20). For pigs, the animal-level seroprevalence of T. gondii was 3.0% (95% CI: 1.60-5.10), while the farm-level, it was 31.6% (95% CI: 12.60-56.60). The PCR-based DNA detection on meat samples from chickens (n = 250) and pork (n = 121) detected 14.0% (95% CI: 9.95-18.9) and 5.8% (95% CI: 2.4-11.6) positive, respectively. Six unique T. gondii haplotypes were isolated from the tissue samples. Multivariable logistic regression analysis showed that feeding the chickens farm-produced feeds and allowing wild animals access to pig farms were significant determinants for farm-level seropositivity. Providing hygienic and good quality feeds to chickens and increasing biosecurity in pig farms through prevention of access by wildlife may reduce the risk of transmission of T. gondii infection in the local chickens and pig farms.

Mechanical and Morphological Changes of the Plantar Flexor Musculotendinous Unit in Children with Unilateral Cerebral Palsy Following 12 Weeks of Plyometric Exercise: A Randomized Controlled Trial.

To investigate how plyometric exercise (PLYO-Ex) affects mechanics and morphometrics of the plantar flexor musculotendinous unit in children with unilateral cerebral palsy, 38 participants (aged 10-16 years) were allocated at random to either the PLYO-Ex group (n = 19; received 24 sessions of plyometric muscle loading, conducted 2 times a week for 3 months in succession) or the control group (n = 19; underwent traditional physical therapy for the same frequency and duration). Measurements were taken pre- and post-intervention. Standard ultrasound imaging was applied to evaluate morphometrics of the gastrocnemius muscle and Achilles tendon unit and an isokinetic dynamometer was used to evaluate maximum voluntary isometric plantar flexors contraction (IVCmax). With controlling for pre-treatment values, significant post-treatment changes favoring the PLYO-Ex group were observed for morphological (tendon (p = 0.003, η2p = 0.23) length; belly length (p = 0.001, η2p = 0.27); tendon thickness (p = 0.035, η2p = 0.35); muscle thickness (p = 0.013, η2p = 0.17); fascicle length (p = 0.009, η2p = 0.18); pennation angle (p = 0.015, η2p = 0.16)) and mechanical and material properties (IVCmax (p = 0.009, η2p = 0.18); tendon's elongation (p = 0.012, η2p = 0.17), stiffness (p = 0.027, η2p = 0.13); stress (p = 0.006, η2p = 0.20); strain (p = 0.004, η2p = 0.21)). In conclusion, plyometric exercise induces significant adaptations within the musculotendinous unit of the plantar flexors in children with unilateral cerebral palsy. These adaptations could improve muscular efficiency and consequently optimize physical/functional performance.

Bardet-Biedl syndrome: a case series.

BACKGROUND: Bardet-Biedl syndrome is a rare multisystem autosomal recessive disorder that falls under the spectrum of ciliopathy disorders. It is characterized by rod-cone dystrophy, renal malformations, polydactyly, learning difficulties, central obesity, and hypogonadism. Many minor features that are related with Bardet-Biedl syndrome might aid in diagnosis and are crucial in clinical management. Bardet-Biedl syndrome is diagnosed on the basis of clinical signs and symptoms, which can be confirmed by genetic testing. Here we present four cases of Bardet-Biedl syndrome. To our knowledge, these are the first cases of Bardet-Biedl syndrome reported from Sudan. CASE PRESENTATION: Here, we report four Sudanese patients who presented with a variety of clinical manifestations of Bardet-Biedl syndrome (two males, 50 and 16 years old; two females, 38 and 18 years old). The first two patients presented with features of chronic kidney disease. The third patient had recently been diagnosed with type 1 diabetes and diabetic ketoacidosis. The fourth patient showed signs of retinal dystrophy early on. Case 1: a 38-year-old female presented with vomiting and irritability; the patient was diagnosed with Bardet-Biedl syndrome as she fulfilled six items of the primary features (obesity, retinitis pigmentosa, post-axial polydactyly, renal abnormalities, learning disabilities, and genitourinary malformations), as well as one secondary feature (cardiovascular involvement, that is, left ventricular hypertrophy). Case 2: a 50-year-old male presented with fatigability; the patient was diagnosed with Bardet-Biedl syndrome as he fulfilled four items of the primary features (obesity, retinitis pigmentosa, post-axial polydactyly, and renal abnormalities) in addition to two secondary features (diabetes mellitus and cardiovascular involvement, that is, left ventricular hypertrophy). Case 3: an 18-year-old female presented with polyuria, polydipsia, weight loss, and epigastric pain for 2 days; the patient was diagnosed with Bardet-Biedl syndrome because he had four major features (retinal dystrophy, post-axial polydactyly, obesity, and learning disabilities) in addition to three secondary features (developmental delay, diabetes mellitus, and strabismus). Case 4: a 16-year-old male presented with a blurring of vision; the patient was diagnosed with Bardet-Biedl syndrome as he exhibited four major features (retinal dystrophy, post-axial polydactyly, obesity, and learning disabilities) plus two secondary features (developmental delay and cataract). CONCLUSION: The scarcity of Bardet-Biedl syndrome necessitates a high index of suspicion to diagnose this syndrome. Increased awareness among physicians is required for the early diagnosis and treatment of Bardet-Biedl syndrome and to avoid complications and mortality.

Mifepristone and misoprostol versus placebo and misoprostol for resolution of miscarriage in women diagnosed with missed miscarriage: the MifeMiso RCT.

TRIAL DESIGN: A randomised, parallel-group, double-blind, placebo-controlled multicentre study with health economic and nested qualitative studies to determine if mifepristone (Mifegyne®, Exelgyn, Paris, France) plus misoprostol is superior to misoprostol alone for the resolution of missed miscarriage. METHODS: Women diagnosed with missed miscarriage in the first 14 weeks of pregnancy were randomly assigned (1 : 1 ratio) to receive 200 mg of oral mifepristone or matched placebo, followed by 800 µg of misoprostol 2 days later. A web-based randomisation system allocated the women to the two groups, with minimisation for age, body mass index, parity, gestational age, amount of bleeding and randomising centre. The primary outcome was failure to pass the gestational sac within 7 days after randomisation. The prespecified key secondary outcome was requirement for surgery to resolve the miscarriage. A within-trial cost-effectiveness study and a nested qualitative study were also conducted. Women who completed the trial protocol were purposively approached to take part in an interview to explore their satisfaction with and the acceptability of medical management of missed miscarriage. RESULTS: A total of 711 women, from 28 hospitals in the UK, were randomised to receive either mifepristone plus misoprostol (357 women) or placebo plus misoprostol (354 women). The follow-up rate for the primary outcome was 98% (696 out of 711 women). The risk of failure to pass the gestational sac within 7 days was 17% (59 out of 348 women) in the mifepristone plus misoprostol group, compared with 24% (82 out of 348 women) in the placebo plus misoprostol group (risk ratio 0.73, 95% confidence interval 0.54 to 0.98; p = 0.04). Surgical intervention to resolve the miscarriage was needed in 17% (62 out of 355 women) in the mifepristone plus misoprostol group, compared with 25% (87 out of 353 women) in the placebo plus misoprostol group (risk ratio 0.70, 95% confidence interval 0.52 to 0.94; p = 0.02). There was no evidence of a difference in the incidence of adverse events between the two groups. A total of 42 women, 19 in the mifepristone plus misoprostol group and 23 in the placebo plus misoprostol group, took part in an interview. Women appeared to have a preference for active management of their miscarriage. Overall, when women experienced care that supported their psychological well-being throughout the care pathway, and information was delivered in a skilled and sensitive manner such that women felt informed and in control, they were more likely to express satisfaction with medical management. The use of mifepristone and misoprostol showed an absolute effect difference of 6.6% (95% confidence interval 0.7% to 12.5%). The average cost per woman was lower in the mifepristone plus misoprostol group, with a cost saving of £182 (95% confidence interval £26 to £338). Therefore, the use of mifepristone and misoprostol for the medical management of a missed miscarriage dominated the use of misoprostol alone. LIMITATIONS: The results from this trial are not generalisable to women diagnosed with incomplete miscarriage and the study does not allow for a comparison with expectant or surgical management of miscarriage. FUTURE WORK: Future work should use existing data to assess and rank the relative clinical effectiveness and safety profiles for all methods of management of miscarriage. CONCLUSIONS: Our trial showed that pre-treatment with mifepristone followed by misoprostol resulted in a higher rate of resolution of missed miscarriage than misoprostol treatment alone. Women were largely satisfied with medical management of missed miscarriage and would choose it again. The mifepristone and misoprostol intervention was shown to be cost-effective in comparison to misoprostol alone. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17405024. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 68. See the NIHR Journals Library website for further project information.

Miscarriage is a common complication of pregnancy, affecting approximately one in four women. Sometimes, medical treatment (i.e. tablets) may be offered to start or speed up the miscarriage process in order for the womb to empty itself. A drug called misoprostol (a tablet that makes the womb contract) is currently recommended for this treatment. However, the addition of another drug called mifepristone [a tablet that reduces pregnancy hormones (Mifegyne^®, Exelgyn, Paris, France)] might help the miscarriage to resolve more quickly. Therefore, we carried out the MifeMiso trial to test if mifepristone plus misoprostol is more effective than misoprostol alone in resolving miscarriage within 7 days. Women were randomly allocated by a computer to receive either mifepristone or placebo, followed by misoprostol 2 days later. Neither the women nor their health-care professionals knew which treatment they received. Some women also talked to the researchers about their experiences of taking part in the study. In total, 711 women were randomised to receive either mifepristone plus misoprostol or placebo plus misoprostol. Overall, 83% of women who received mifepristone plus misoprostol had miscarriage resolution within 7 days, compared with 76% of the women who received a placebo plus misoprostol. Surgery was required less often in women who received mifepristone plus misoprostol: 17% of women who received it required surgery, compared with 25% of women who received the placebo. Treatment with mifepristone did not appear to have any negative effects. Treatment with mifepristone plus misoprostol was more cost-effective than misoprostol alone, with an average saving of £182 per woman. Having taken part in the study, most women would choose medical management again and would recommend it to someone they knew who was experiencing a miscarriage.

Survey of antibodies to Rift Valley fever virus and associated risk factors in one-humped camels (Camelus dromedarius) slaughtered in Maiduguri abattoir, Borno State, Nigeria.

Rift Valley fever (RVF) is an emerging mosquito-borne zoonosis that threatens public health and animal agriculture in the endemic areas causing devastating epizootics characterized by abortion storms and high mortalities, especially in newborn animals. A cross-sectional study was conducted to determine the seroprevalence and investigate risk factors associated with exposure to the virus in camels slaughtered in Maiduguri abattoir, Borno State of Nigeria. Camels presented for slaughtered were sampled and data on age, sex, source or origin, utility, presence of post-mortem lesions, body weights and body condition score were collected. Blood samples were collected and sera were harvested and stored at - 20 °C until tested. The sera were tested using a commercial ELISA kit based on the manufacturer's instructions. The overall seroprevalence in the study was 20.7% (95% CI, 13.6-30.0). The analysis showed no significant differences between the presence of antibodies and variables that included the sex of camels (χ2 = 0.015, df = 1, p = 0.904) and the presence of post-mortem lesion on the carcass (χ2 = 0.009, df = 1, p = 0.925). There were significant differences between presence of antibodies and three variables that included the age (χ2 = 4.89, df = 1, p = 0.027), the source (χ2 = 7.077, df = 2, p = 0.029) and the main utility (χ2 = 8.057, df = 3, p = 0.045) of the camels. It was concluded that camels presented for slaughter at the Maiduguri abattoir have evidence of exposure to the RVF virus and maybe means of transmission of the virus. Regular monitoring and control of transboundary animal movements were recommended in the study area.

Change in microbial profile and environmental conditions in a constructed wetland system treating greywater.

The objective of this work was to verify the relationships between environmental conditions and microbial processes along a raw-light greywater flow in an improved constructed wetland (CW) system. Physicochemical analysis and high-throughput DNA sequencing were performed in the different zones to investigate the environmental conditions and microbial communities. The results showed that the system operated predominantly under anaerobic conditions, with redox potential (Eh) increasing from the inlet (-342.9 mV) to the outlet (-316.4 mV). Conversely, the chemical oxygen demand (COD) decreased along the greywater flow, suggesting negative correlation between these characteristics. The zones of the evapotranspiration and treatment tank (CEvaT) were characterized by lower community diversity and richness and by the presence of specific groups: Proteobacteria and Synergistetes related to the first steps of the conversion of organic carbon, in the bottom layer inside the anaerobic chamber (AnC); methanogens (Methanosaeta and Methanobacterium) and sulphate-reducing bacteria (Desulfovibrio, Desulforhabdus and Desulfomonile) in the middle layer; and microorganisms associated with the nitrogen cycle and oxygen release (Acinetobacter, Novosphingobium, Candidatus Nitrososphaera) in the top layer. On the other hand, the increase of the ORP and decrease of organic matter concentrations were associated with higher community diversity and richness in the middle layer of the CW, which showed higher abundance of microorganisms involved in methane (Methylobacterium and Candidatus Koribacter) and sulphur (Rhodoblastus and Thiobacillus) oxidation.

Achieving Fair Load Balancing by Invoking a Learning Automata-Based Two-Time-Scale Separation Paradigm.

In this article, we consider the problem of load balancing (LB), but, unlike the approaches that have been proposed earlier, we attempt to resolve the problem in a fair manner (or rather, it would probably be more appropriate to describe it as an ϵ -fair manner because, although the LB can, probably, never be totally fair, we achieve this by being "as close to fair as possible"). The solution that we propose invokes a novel stochastic learning automaton (LA) scheme, so as to attain a distribution of the load to a number of nodes, where the performance level at the different nodes is approximately equal and each user experiences approximately the same Quality of the Service (QoS) irrespective of which node that he/she is connected to. Since the load is dynamically varying, static resource allocation schemes are doomed to underperform. This is further relevant in cloud environments, where we need dynamic approaches because the available resources are unpredictable (or rather, uncertain) by virtue of the shared nature of the resource pool. Furthermore, we prove here that there is a coupling involving LA's probabilities and the dynamics of the rewards themselves, which renders the environments to be nonstationary. This leads to the emergence of the so-called property of "stochastic diminishing rewards." Our newly proposed novel LA algorithm ϵ -optimally solves the problem, and this is done by resorting to a two-time-scale-based stochastic learning paradigm. As far as we know, the results presented here are of a pioneering sort, and we are unaware of any comparable results.

Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone. METHODS: MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 µg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/m2vs ≥35 kg/m2), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024. FINDINGS: Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups. INTERPRETATION: Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Giant Encephalocele in Sokoto, Nigeria: A 5-Year Review of Operated Cases.

OBJECTIVE: Encephalocele is a common congenital malformation of the central nervous system; however, giant encephaloceles are rare. The use of folic acid supplementation and termination of pregnancies, which are prenatally diagnosed with encephaloceles and other congenital malformation of the central nervous system, has significantly reduced the occurrence of this type of congenital malformation, especially in developed countries. METHODS: This was a retrospective review over a 5-year period from January 2006 to December 2010 at the Department of Neurosurgery, Regional Centre for Neurosurgery, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria. The records of patients with giant encephalocele were retrieved from the case notes of patients who had excision and repair for encephalocele. RESULTS: Seventy-three patients had excision and repair of encephalocele over the study period. However, the records of only 50 patients were retrieved. Fourteen (28%) of the 50 whose records were retrieved had giant encephalocele. There were 4 male and 10 female patients (1:2.5). Thirteen (92.9%) had the lesion located in the occipital region, whereas in 1 patient (7.1%) the lesion was at the vertex. Three (21%) of the cases had microcephaly, 1 (7.1%) had macrocephaly, and 1 (7.1%) developed postoperative hydrocephalus. The average size of defect was 2.43 cm, and the size of the lesion ranged from 12 × 6 cm to 40 × 50 cm. The average maternal age was 20.3 years (n = 6), and the paternal age was 29 years (n = 4). Four out of 7 (57%) mothers had febrile illness in early pregnancy. Seven out of 10 patients (70%) did not have antenatal care. CONCLUSIONS: This condition is more common in children conceived during the period when farm products are yet to be harvested, and whose mothers did not attend antenatal care visits. It is recommended that mothers should be educated on the necessity of preconception folic acid. Implementation of a national strategy on food fortification is also advised. We recommend surgery after the first month of life to reduce poor early postoperative outcomes. In developing countries and centers with suboptimal pediatric intensive care units, surgical intervention is preferred after the first month of life with good temperature control, adequate fluid replacement following rupture of the sac, blood transfusion availability, and, only if necessary, complex cranial reconstruction.

Semi-continuous production of the anticancer drug taxol by Aspergillus fumigatus and Alternaria tenuissima immobilized in calcium alginate beads.

Taxol is the most profitable drug ever developed in cancer chemotherapy; however, the market demand for the drug greatly exceeds the supply that can be sustained from its natural sources. In this study, Aspergillus fumigatus TXD105-GM6 and Alternaria tenuissima TER995-GM3 were immobilized in calcium alginate beads and used for the production of taxol in shake flask cultures. In an effort to increase the taxol magnitude, immobilization conditions were optimized by response surface methodology program (RSM). The optimum levels of alginate concentration, calcium chloride concentration, and mycelium fresh weight were 5%, 4%, and 15% (w/v), respectively. Under these conditions, taxol production by the respective fungal strains was intensified to 901.94 µg L-1 and 529.01 µg L-1. Moreover, the immobilized mycelia of both strains were successfully used in the repeated production of taxol for six different fermentation cycles. The total taxol concentration obtained in all cycles reached 4540.14 µg L-1 by TXD105-GM6 and 2450.27 µg L-1 by TER995-GM3 strain, which represents 7.85- and 6.31-fold increase, as compared to their initial titers. This is the first report on the production of taxol in semi-continuous fermentation. To our knowledge, the taxol productivity achieved in this study is the highest reported by academic laboratories for microbial cultures which indicates the future possibility to reduce the cost of taxol production.

Strain improvement and immobilization technique for enhanced production of the anticancer drug paclitaxel by Aspergillus fumigatus and Alternaria tenuissima.

UV and gamma irradiation mutagenesis was applied on Aspergillus fumigatus and Alternaria tenuissima in order to improve their producing ability of paclitaxel. Among the screened mutants, two stable strains (designated TXD105-GM6 and TER995-GM3) showed the maximum paclitaxel production. Paclitaxel titers of the two respective mutants were dramatically intensified to 1.22- and 1.24-fold, as compared by their respective parents. Immobilization using five different entrapment carriers of calcium alginate, agar-agar, Na-CMC, gelatin, and Arabic gum was successfully applied for production enhancement of paclitaxel by the two mutants. The immobilized cultures were superior to free-cell cultures and paclitaxel production by the immobilized mycelia was much higher than that of the immobilized spores using all the tried carriers. Moreover, calcium alginate gel beads were found the most conductive and proper entrapment carrier for maximum production of paclitaxel. The feasibility of the paclitaxel production by the immobilized mycelia as affected by incubation period, medium volume, and number of beads per flask was adopted. Under the favorable immobilization conditions, the paclitaxel titers were significantly intensified to 1.31- and 1.88-fold by the respective mutants, as compared by their free cultures. The obtained paclitaxel titers by the immobilized mycelia of the respective mutants (694.67 and 388.65 µg L-1) were found promising in terms of fungal production of paclitaxel. Hence, these findings indicate the future possibility to reduce the cost of producing paclitaxel and suggest application of the immobilization technique for the biotechnological production of paclitaxel at an industrial scale.

Thulium laser enucleation of the prostate (ThuLEP): Results, complications, and risk factors in 139 consecutive cases.

OBJECTIVES: To report our experience with the emerging technique of thulium laser enucleation of the prostate (ThuLEP) for the treatment for prostate hyperplasia. PATIENTS AND METHODS: Our inclusion criteria were an International Prostate Symptom Score (IPSS) of >15 and a quality-of-life (QoL) score of >3 in patients with confirmed bladder outflow obstruction, no longer responsive to medical therapy, with a significant post-void residual urine volume (PVR; >100 mL), with or without recurrent urinary tract infection and/or acute urinary retention. Patients with neurogenic bladder, urethral strictures, bladder stones, and previously failed transurethral prostate surgery were excluded. RESULTS: In all, 139 men were included in the study. The mean age was 67.8 years. The IPSS and QoL score improved by 17.6 and 2.6, respectively. The flow rate increased from a mean of 9.6 mL to 31.2 mL and the PVR decreased from a mean of 131 mL to 30 mL. On univariate and multivariate analyses, operating time was a predictive factor for haemoglobin drop during the operation. Heparin prophylaxis was the only risk factor identified for postoperative bleeding. Two patients (0.01%) required blood transfusion. One patient (0.007%) required re-intervention for bleeding control, and two patients developed urethral and bladder neck strictures (0.01%). CONCLUSION: ThuLEP is safe and reproducible. Whilst it significantly reduces intraoperative bleeding as compared to transurethral resection of the prostate, operating time and perioperative heparin prophylaxis may still lead to a Hb drop and constitute a risk factor for postoperative bleeding. Therefore, a potential risk of deep vein thrombosis requiring heparin prophylaxis should be carefully considered and balanced with the expected clinical benefit of the operation.

The relationship between bacterial sources and genotype to the antimicrobial resistance pattern of Burkholderia pseudomallei.

BACKGROUND: Melioidosis is a fatal emerging infectious disease of both man and animal caused by bacteria Burkholderia pseudomallei. Variations were suggested to have existed among the different B. pseudomallei clinical strains/genotypes which may implicate bacterial susceptibility and resistance toward antibiotics. AIM: This study was designed to determine whether the phenotypic antibiotic resistance pattern of B. pseudomallei is associated with the source of isolates and the genotype. MATERIALS AND METHODS: A collection of 111 B. pseudomallei isolates from veterinary cases of melioidosis and the environments (soil and water) were obtained from stock cultures of previous studies and were phylogenetically characterized by multilocus sequence typing (ST). The susceptibility to five antibiotics, namely meropenem (MEM), imipenem, ceftazidime (CAZ), cotrimoxazole (SXT), and co-amoxiclav (AMC), recommended in both acute and eradication phases of melioidosis treatment were tested using minimum inhibitory concentration antibiotics susceptibility test. RESULTS: Majority of isolates were susceptible to all antibiotics tested while few resistant strains to MEM, SXT, CAZ, and AMC were observed. Statistically significant association was found between resistance to MEM and the veterinary clinical isolates (p<0.05). The likelihood of resistance to MEM was significantly higher among the novel ST 1130 isolates found in veterinary cases as compared to others. CONCLUSION: The resistance to MEM and SXT appeared to be higher among veterinary isolates, and the novel ST 1130 was more likely to be resistant to MEM as compared to others.

Surgical motion analysis using discriminative interpretable patterns.

OBJECTIVE: The analysis of surgical motion has received a growing interest with the development of devices allowing their automatic capture. In this context, the use of advanced surgical training systems makes an automated assessment of surgical trainee possible. Automatic and quantitative evaluation of surgical skills is a very important step in improving surgical patient care. MATERIAL AND METHOD: In this paper, we present an approach for the discovery and ranking of discriminative and interpretable patterns of surgical practice from recordings of surgical motions. A pattern is defined as a series of actions or events in the kinematic data that together are distinctive of a specific gesture or skill level. Our approach is based on the decomposition of continuous kinematic data into a set of overlapping gestures represented by strings (bag of words) for which we compute comparative numerical statistic (tf-idf) enabling the discriminative gesture discovery via its relative occurrence frequency. RESULTS: We carried out experiments on three surgical motion datasets. The results show that the patterns identified by the proposed method can be used to accurately classify individual gestures, skill levels and surgical interfaces. We also present how the patterns provide a detailed feedback on the trainee skill assessment. CONCLUSIONS: The proposed approach is an interesting addition to existing learning tools for surgery as it provides a way to obtain a feedback on which parts of an exercise have been used to classify the attempt as correct or incorrect.

Physicochemical properties associated with the presence of Burkholderia pseudomallei in small ruminant farm water supplies in Peninsular Malaysia.

Burkholderia pseudomallei causes melioidosis, a life-threatening infection in both humans and animals. Water is an important reservoir of the bacteria and may serve as a source of environmental contamination leading to infection. B. pseudomallei has an unusual ability to survive in water for a long period. This paper investigates physicochemical properties of water associated with the presence of B. pseudomallei in water supply in small ruminant farms in Peninsular Malaysia. Physicochemical properties of water samples taken from small ruminant farms that included temperature, pH, dissolved oxygen (DO2), optical density (OD), and chemical oxygen demand (COD) were measured after which the samples were cultured for B. pseudomallei. Multivariable logistic regression model revealed that slightly acidic water pH and higher COD level were significantly associated with the likelihood of the B. pseudomallei presence in the water.

Phylogenetic Diversity of Burkholderia pseudomallei isolated from veterinary cases and the environments in Peninsular Malaysia.

This study was designed to determine the genotype and the phylogeny of Burkholderia pseudomallei isolated from veterinary cases and from the animal environments in Peninsular Malaysia. The Malaysian B. pseudomallei population were then compared to those found elsewhere. A total of 113 isolates from veterinary cases (35) and the environment (56 from soil and 22 from water) were characterized using multilocus sequence typing (MLST). Two novel alleles, allele 97 and 69 of the gene locus ace and lepA respectively were recovered. Isolates were resolved into 12 distinct sequence types (STs) out of which five were novel, namely ST1130, ST1131, ST1338, ST1339 and ST1367. The isolates from veterinary cases co-clustered with those from the environment. B. pseudomallei isolates in this study were highly clonal and have descended from a common ancestor clonal complex (CC) 48 found in Southeast Asia. This study shows that veterinary case isolates are often caused by similar STs, with similar populations found in the direct animal environment and those previously reported to cause human infections in Malaysia and elsewhere. Isolates of B. pseudomallei from human infections have been given more attention, with a comparatively lower focus on isolates from animals and the farm environment. This study highlighted the genotype and phylogeny of B. pseudomallei isolated from animals and the environment and their relations to the isolates from human cases reported in Malaysia and elsewhere. Most STs reported in this study, from veterinary cases and animal environment are similar to those previously reported as causing human infections in Malaysia and elsewhere. Therefore, even though direct zoonosis is uncommon, monitoring melioidosis occurrences in animals can provide insights on the bacterial strains infecting humans.

Odorant-odorant metabolic interaction, a novel actor in olfactory perception and behavioral responsiveness.

In the nasal olfactory epithelium, olfactory metabolic enzymes ensure odorant clearance from the olfactory receptor environment. This biotransformation of odorants into deactivated polar metabolites is critical to maintaining peripheral sensitivity and perception. Olfactory stimuli consist of complex mixtures of odorants, so binding interactions likely occur at the enzyme level and may impact odor processing. Here, we used the well-described model of mammary pheromone-induced sucking-related behavior in rabbit neonates. It allowed to demonstrate how the presence of different aldehydic odorants efficiently affects the olfactory metabolism of this pheromone (an aldehyde too: 2-methylbut-2-enal). Indeed, according to in vitro and ex vivo measures, this metabolic interaction enhances the pheromone availability in the epithelium. Furthermore, in vivo presentation of the mammary pheromone at subthreshold concentrations efficiently triggers behavioral responsiveness in neonates when the pheromone is in mixture with a metabolic challenger odorant. These findings reveal that the periphery of the olfactory system is the place of metabolic interaction between odorants that may lead, in the context of odor mixture processing, to pertinent signal detection and corresponding behavioral effect.

Production of paclitaxel with anticancer activity by two local fungal endophytes, Aspergillus fumigatus and Alternaria tenuissima.

Among 60 fungal endophytes isolated from twigs, bark, and mature leaves of different plant species, two fungal isolates named TXD105 and TER995 were capable of producing paclitaxel in amounts of up to 84.41 and 37.92 µg L-1, respectively. Based on macroscopic and microscopic characteristics, ITS1-5.8S-ITS2 rDNA sequence, and phylogenetic characteristic analysis, the two respective isolates were identified as Aspergillus fumigatus and Alternaria tenuissima. In the effort to increase paclitaxel magnitude by the two fungal strains, several fermentation conditions including selection of the proper fermentation medium, agitation rate, incubation temperature, fermentation period, medium pH, medium volume, and inoculum nature (size and age of inoculum) were tried. Fermentation process carried out in M1D medium (pH 6.0) and maintained at 120 rpm for 10 days and at 25 °C using 4% (v/v) inoculum of 5-day-old culture stimulated the highest paclitaxel production to attain 307.03 µg L-1 by the A. fumigatus strain. In the case of the A. tenuissima strain, fermentation conditions conducted in flask basal medium (pH 6.0) and maintained at 120 rpm for 14 days and at 25 °C using 8% (v/v) inoculum of 7-day-old culture were found the most favorable to attain the highest paclitaxel production of 124.32 µg L-1. Using the MTT-based assay, fungal paclitaxel significantly inhibited the proliferation of five different cancer cell lines with 50% inhibitory concentration values varied from 3.04 to 14.8 µg mL-1. Hence, these findings offer new and alternate sources with excellent biotechnological potential for paclitaxel production by fungal fermentation.