Identifying pollution dynamics using discrete Fourier transform: From an urban-rural river, Central Mexico.

The quality of life and human survival is dependent on sustainable development and sanitation of water bodies in an environment. The present research focuses on cyclicity data of more than 750,000 records of parameters associated with the water quality from a rural-urban river monitoring stations in real-time from River Atoyac in Central Mexico. The events detected in the instrumental records correlated with 2528 laboratory and instrumental determinations. The 64 polluting compounds were grouped into inorganic compounds (metals and metalloids) and organic compounds (pesticides, herbicides, hydrocarbons). Metal associated compounds were grouped along mechanical, pharmaceutical and textile industries which associates itself with the entry of polluting components. The cyclicity of the events was detected through Discrete Fourier Transformation time series analysis identifying the predominant events in each station. These highlight the events at 23-26 h corresponding to a circadian pattern of the metabolism of the city. Likewise, pollution signals were detected at 3.3, 5.5, and 12-14 h, associated with discharges from economic activities. Multivariate statistical techniques were used to identify the circadian extremes of a regionalized cycle of polluting compounds in each of the stations. The results of this research allow pollution prevention using a mathematical analysis of time series of different quality parameters collected at monitoring stations in real-time as a tool for predicting polluting events. The DFT analysis makes it possible to prevent polluting events in different bodies of water, allowing to support the development of public policies based on the supervision and control of pollution.

Female Urgency, Trial of Urodynamics as Routine Evaluation (FUTURE study): a superiority randomised clinical trial to evaluate the effectiveness and cost-effectiveness of invasive urodynamic investigations in management of women with refractory overactive bladder symptoms.

BACKGROUND: Overactive bladder (OAB) syndrome is a symptom complex affecting 12-14% of the UK adult female population. Symptoms include urinary urgency, with or without urgency incontinence, increased daytime urinary frequency and nocturia. OAB has a negative impact on women's social, physical, and psychological wellbeing. Initial treatment includes lifestyle modifications, bladder retraining, pelvic floor exercises and pharmacological therapy. However, these measures are unsuccessful in 25-40% of women (refractory OAB). Before considering invasive treatments, such as Botulinum toxin injection or sacral neuromodulation, most guidelines recommend urodynamics to confirm diagnosis of detrusor overactivity (DO). However, urodynamics may fail to show evidence of DO in up to 45% of cases, hence the need to evaluate its effectiveness and cost-effectiveness. FUTURE (Female Urgency, Trial of Urodynamics as Routine Evaluation) aims to test the hypothesis that, in women with refractory OAB, urodynamics and comprehensive clinical assessment is associated with superior patient-reported outcomes following treatment and is more cost-effective, compared to comprehensive clinical assessment only. METHODS: FUTURE is a pragmatic, multi-centre, superiority randomised controlled trial. Women aged ≥ 18 years with refractory OAB or urgency predominant mixed urinary incontinence, and who have failed/not tolerated conservative and medical treatment, are considered for trial entry. We aim to recruit 1096 women from approximately 60 secondary/tertiary care hospitals across the UK. All consenting women will complete questionnaires at baseline, 3 months, 6 months and 15 months post-randomisation. The primary outcome is participant-reported success at 15 months post-randomisation measured using the Patient Global Impression of Improvement. The primary economic outcome is incremental cost per quality-adjusted life year gained at 15 months. The secondary outcomes include adverse events, impact on other urinary symptoms and health-related quality of life. Qualitative interviews with participants and clinicians and a health economic evaluation will also be conducted. The statistical analysis of the primary outcome will be by intention-to-treat. Results will be presented as estimates and 95% CIs. DISCUSSION: The FUTURE study will inform patients, clinicians and policy makers whether routine urodynamics improves treatment outcomes in women with refractory OAB and whether it is cost-effective. TRIAL REGISTRATION: ISRCTN63268739 . Registered on 14 September 2017.

Stress in Parents of Children With Genetically Determined Leukoencephalopathies: A Pilot Study.

Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoencephalopathies, aged 1 month to 12 years. Thirty-four mothers and 21 fathers completed the Parenting Stress Index-4th Edition. One demographic questionnaire was completed per family. Detailed clinical data was gathered on all patients. Statistical analysis was performed with total stress percentile score as the primary outcome. Mothers and fathers had significantly higher stress levels compared with the normative sample; 20% of parents had high levels of stress whereas 11% had clinically significant levels of stress. Mothers and fathers had comparable total stress percentile scores. We identified pediatric behavioral difficulties and gross motor function to be factors influencing stress in mothers. Our study is the first to examine parental stress in this population and highlights the need for parental support early in the disease course. In this pilot study, we demonstrated that using the Parenting Stress Index-4th Edition to assess stress levels in parents of patients with genetically determined leukoencephalopathies is feasible, leads to valuable and actionable results, and should be used in larger, prospective studies.

Recessive Mutations in POLR3B Encoding RNA Polymerase III Subunit Causing Diffuse Hypomyelination in Patients with 4H Leukodystrophy with Polymicrogyria and Cataracts.

The diagnosis of 4H leukodystrophy (hypomyelination, hypogonadotropic hypogonadism, and hypodontia) is based on clinical findings and magnetic resonance imaging (MRI). Recently, mutations of the genes encoding Pol III (RNA polymerase III) subunit A (POLR3A) and subunit B (POL3B) have been identified as the genetic causes of hypomyelination. We describe two Polish female siblings aged 5 and 10 years with compound heterozygous mutations in POLR3B. They both presented with similar clinical symptoms and MRI findings presenting as 4H leukodystrophy, and the association of polymicrogyria and cataract. According to our observation in young children with the absence of hypogonadotropic hypogonadism, brain MRI pattern is very essential in proper early diagnosis of 4H leukodystrophy. All clinical and radiological results are of course helpful, however genetic conformation is always necessary.

Comparison of a new metamizole formulation and carprofen for extended post-operative analgesia in dogs undergoing ovariohysterectomy.

A newly developed slow-release tablet formulation of metamizole was compared with carprofen for post-operative analgesia in dogs undergoing ovariohysterectomy. Twenty-three dogs were randomly assigned to one of two groups, and administered 50 mg/kg metamizole PO (Group M) or 4 mg/kg carprofen PO (Group C) 1 h before anaesthetic induction and 24 and 48 h later. Anaesthesia was induced with propofol and maintained with isoflurane and fentanyl, after premedication with 0.005 mg/kg medetomidine and 0.3 mg/kg methadone IM. A blinded observer assessed post-operative sedation, and analgesia using a visual analogue scale, a dynamic interactive visual analogue scale, the Glasgow composite pain scale (GCPS), and a mechanical nociceptive threshold device (T = 0.5, 1, 2, 4, 8, 12, 18, 21, 24, 36, 45, 60 and 70 h after surgery). Rescue methadone was administered if the GCPS was >6/24 in ambulatory dogs, or >5/20 in non-ambulatory dogs. Plasma concentrations of test drugs were quantified. The dose range for metamizole was 39-56 mg/kg. At T = 0.5 h sedation scores were significantly higher in Group C and GCPS scores were significantly higher in Group M. Three dogs required rescue methadone (Group M, n = 1; Group C, n = 2). Vomiting occurred post-operatively in 45% of dogs in Group M. Carprofen and metamizole were both well absorbed; peak concentrations occurred within 4-24 h, and 4-16 h for carprofen and metamizole, respectively. Both drugs provided adequate analgesia of similar duration. No side effects were observed with carprofen while vomiting was frequent following administration of metamizole.

Incidence of delayed hair re-growth, pruritus, and urinary retention after epidural anaesthesia in dogs.

OBJECTIVE: Delayed hair re-growth, pruritus and urinary retention are known complications after epidural anaesthesia in dogs. The aim of this study was to prospectively evaluate the effect of epidurally administered drugs on the occurrence of these complications in dogs. MATERIAL AND METHODS: Ninety dogs were included in this study. Eighty client-owned dogs undergoing surgery were randomly assigned to one of three epidural treatment groups: either morphine and bupivacaine (MB), bupivacaine (B), or saline solution 0.9% (S) was administered epidurally to these patients. Ten dogs were only clipped in the lumbosacral area (C). Follow-up started 4 weeks after clipping and was performed every 4-5 weeks in cases of delayed hair re-growth or pruritus. Hair re-growth in the lumbosacral area was observed and compared to hair re-growth in the surgical field and the fentanyl patch area. Cytological analysis and a trichogram were performed if hair re-growth was delayed after 6 months. Time interval to first urination postoperatively was recorded (n = 80). RESULTS: Hair re-growth was delayed in 11 dogs (12.2%; B: n = 7, S: n = 2, MB: n = 1, C: n = 1) with no differences between groups. Pruritus was evident in two dogs (2.2%; MB: n = 1, S: n = 1). After 6 months, hair had started to re-grow in all but one dog (B). After 10 months the coat of this dog had re-grown. Time to first urination did not differ between groups. CONCLUSION AND CLINICAL RELEVANCE: No direct correlation between the particular drugs injected epidurally and delayed hair re-growth, pruritus and urinary retention could be shown. Dog owners should be informed that hair re-growth after epidural anaesthesia could be markedly delayed.

Trends in obstetric anal sphincter injuries over 10 years.

Obstetric anal sphincter injuries (OASIS) is a known complication of vaginal delivery and has significant public health issues, as it can cause both short- and long-term morbidity in women. The most commonly reported complications include different grades of faecal/flatus incontinence, pain and sexual dysfunction. In our study, we found a rising trend in OASIS rates in vaginal deliveries, with the rising rate of forceps and the falling rate of SVD, which is at least partly due to increased awareness and training in OASIS. However, there is an actual increase in the number of such tears at vaginal deliveries. Midwifery and obstetric practices have certainly changed over the last decade and we discuss the possible factors, which might be contributing to such a rise.

A randomised controlled trial comparing TVT, Pelvicol and autologous fascial slings for the treatment of stress urinary incontinence in women.

OBJECTIVE: To compare TVT(TM) , Pelvicol(TM) and autologous fascial slings (AFSs). DESIGN: A multicentre randomised control trial. SETTING: Four units in the UK. POPULATION: Women requiring primary surgery for stress urinary incontinence (SUI). METHODS: A total of 201 women with urodynamically proven stress incontinence were randomised into three groups and assessed at baseline, 6 weeks, 6 months and 1 year. MAIN OUTCOME MEASURE: The primary outcome was patient-reported improvement rates. Secondary outcomes included operative complications/time, intermittent self-catheterisation (ISC) and re-operation rates. The quality-of-life tools used were the Bristol Female Lower Urinary Tract Symptoms (BFLUTS) and EuroQoL. RESULTS: Fifty women had a Pelvicol(TM) sling, 79 had AFSs and 72 had TVT(TM). At 6 months the Pelvicol(TM) arm had poorer improvement rates (73%) than TVT(TM) (92%)/AFS (95%); P=0.003. At 1 year only 61% of the Pelvicol(TM) slings remained as improved, versus 93% of TVTs and 90% of AFSs (P<0.001). Pelvicol(TM) has poorer dry rates (22%) than TVT(TM) (55%)/AFS (48%) (P=0.001) at 1 year; hence, the Pelvicol(TM) arm was suspended following interim analysis. There is no difference in the success rates between TVT(TM) and AFS. One in five women in the Pelvicol(TM) arm had further surgery for SUI by 1 year, but none required further surgery in the other arms. AFS took longer to do (54 minutes versus 35 minutes for TVT(TM) /36 minutes for Pelvicol(TM) ) and had higher ISC rates (9.9 versus 0% Pelvicol(TM) /TVT(TM) 1.5%). Hospital stay was shortest for TVT(TM) (2 days). Most BFLUTS domains showed improvement in all three arms. The improvement for women in the Pelvicol(TM) arm, however, was less than for women in the other arms in several key domains. CONCLUSIONS: Pelvicol(TM) cannot be recommended for the management of SUI. TVT(TM) does not have greater efficacy than AFS, but does utilise fewer resources.

Antenatal pelvic floor exercises: a survey of both patients' and health professionals' beliefs and practice.

The aim was to discover how often women perform pelvic floor exercises (PFE) in the antenatal period and how they wished to be taught. We compared this with the opinions of the health professionals looking after them. A total of 54 women attending the antenatal day assessment unit completed questionnaires. A total of 21 obstetricians, 29 midwives and 25 GPs returned similar questionnaires. Most women think they should be performing PFE daily but only 15% do so. Some 57% of the women wanted to be taught in the antenatal period. Over 50% of the women/midwives believed that PFE should be taught in an individual basis. Obstetricians/GPs favoured classes. A total of 76% of the women want midwives to teach them PFE and 57% of midwives agree. Most health professionals felt that they had not received adequate training on PFE. The midwife is felt to be the best placed person to teach PFE. Health professionals give PFE low priority.

A randomised controlled trial comparing two autologous fascial sling techniques for the treatment of stress urinary incontinence in women: short, medium and long-term follow-up.

This randomised control trial compares full-length autologous slings (Group A: 81 women) with a modified "sling-on-a-string" (Group B: 84 women) technique for the treatment of stress urinary incontinence (SUI). Primary outcomes are quality of life (QoL) scores; Group A/Group B. The IIQ-7 scores decrease from 1.91/1.85 at baseline to 0.65/0.72 at 12 months and 0.85/0.92 at +5 years. The UDI-6 scores decrease from 1.85/1.61 at baseline to 0.66/0.62 at 12 months and 1.22/1.08 at +5 years. The incidence of SUI is 13% at 3 months but averages 53% at +5 years. Both techniques offer similar improvements. The shorter sling is quicker, less painful and with less hospital readmissions. The 'sling-on-a-string' technique is as effective as the standard technique with better short-term sequelae. The incidence of SUI post-autologous slings rises over the long term.

Botulinum toxin B is not an effective treatment of refractory overactive bladder.

OBJECTIVES: To determine the efficacy and safety of botulinum toxin-B (BTX-B) in two groups of patients with urodynamically proven idiopathic detrusor overactivity (IDO) or neurogenic DO (NDO) refractory to conservative treatment. METHODS: This was a nonrandomized, prospective study. We diluted 5000 U of BTX-B in 20 mL of normal saline and injected it at 20 sites around the bladder, avoiding the trigone. The data collected at recruitment and 10 and 26 weeks postoperatively included number of incontinent episodes, frequency, and nocturia, King's Health Questionnaire score, and the urodynamic parameters of volume at the first overactive contraction and maximal cystometric capacity. RESULTS: A total of 25 patients were recruited, 20 with IDO and 5 with NDO. Only 7 patients, all with IDO, reported symptomatic improvement at the 10-week assessment. The symptoms had returned in these 7 patients at a median of 136 days (range 106 to 151) after injection. Of the remaining 20 patients, 16 (13 with IDO and 3 with NDO) thought an initial improvement had occurred but it had worn off or was wearing off by the first assessment. Two patients (both with NDO) reported no improvement. CONCLUSIONS: BTX-B had a limited duration of action, with most of its symptomatically beneficial effects wearing off by 10 weeks in most of our patients. The short duration of action for BTX-B suggests it is unlikely to gain widespread use in the treatment of DO.

Intravesical oxybutynin: practicalities of clinical use.

Oral anticholinergic therapy, used for the treatment of detrusor overactivity (DO), is limited by systemic side-effects and because of failure to respond. Alternative routes of administration include the intravesical route. We reviewed 11 women who were treated with intravesical oxybutynin (IVO). All had idiopathic DO, their symptoms having been unsuccessfully controlled on oral agents. Seven patients had symptomatic improvement. Six out of the eight patients that completed their voiding diaries showed a reduction in voiding frequency. Five patients found the procedure too inconvenient. Seven patients suffered chemical irritation. One patient complained of voiding difficulties. No patient reported systemic side-effects. The mean duration of treatment was 4-5 weeks; two patients continue to use IVO. IVO can be used successfully in the treatment of DO, but its use is limited due to the inconvenience related to catheterisation. With the advent of Botox and oxybutynin patches, IVO probably has a limited role.

Functional coupling as a basic mechanism of feedback regulation of cardiac energy metabolism.

In this review we analyze the concepts and the experimental data on the mechanisms of the regulation of energy metabolism in muscle cells. Muscular energetics is based on the force-length relationship, which in the whole heart is expressed as a Frank-Starling law, by which the alterations of left ventricle diastolic volume change linearly both the cardiac work and oxygen consumption. The second basic characteristics of the heart is the metabolic stability--almost constant levels of high energy phosphates, ATP and phosphocreatine, which are practically independent of the workload and the rate of oxygen consumption, in contrast to the fast-twitch skeletal muscle with no metabolic stability and rapid fatigue. Analysis of the literature shows that an increase in the rate of oxygen consumption by order of magnitude, due to Frank-Starling law, is observed without any significant changes in the intracellular calcium transients. Therefore, parallel activation of contraction and mitochondrial respiration by calcium ions may play only a minor role in regulation of respiration in the cells. The effective regulation of the respiration under the effect of Frank-Starling law and metabolic stability of the heart are explained by the mechanisms of functional coupling within supramolecular complexes in mitochondria, and at the subcellular level within the intracellular energetic units. Such a complex structural and functional organisation of heart energy metabolism can be described quantitatively by mathematical models.

Active/inactive state transitions of the chloroplast F1 ATPase are induced by a slow binding and release of Mg2+. Relationship to catalysis and control of F1 ATPases.

Mg2+ is known to be a potent inhibitor of F1 ATPases from various sources. Such inhibition requires the presence of a tightly bound ADP at a catalytic site. Results with the spinach chloroplast F1 ATPase (CF1) show that the time delays of up to 1 min or more in the induction or the relief of the inhibition are best explained by a slow binding and slow release of Mg2+ rather than by slow enzyme conformational changes. CF1 is known to have multiple Mg2+ binding sites with Kd values in the micromolar range. The inhibitory Mg2+ and ADP can bind independently to CF1. When Mg2+ and ATP are added to the uninhibited enzyme, a relatively fast rate of hydrolysis attained soon after the addition is followed by a much slower steady-state rate. The inhibited steady-state rate results from a slowly attained equilibrium of binding of medium Mg2+. The Kd for the binding of the inhibitory Mg2+ is in the range of 1-8 microM, in the presence or absence of added ATP, as based on the extent of rate inhibition induced by Mg2+. Assessments from 18O exchange experiments show that the binding of Mg2+ is accompanied by a relatively rapid change to an enzyme form that is incapable of hydrolyzing MgATP. When ATP is added to the Mg2+- and ADP-inhibited enzyme, the resulting reactivation can be explained by MgATP binding to an alternate catalytic site which results in a displacement of the tightly bound ADP after a slow release of Mg2+. Both an increase in temperature (to 50 degrees C) and the presence of activating anions such as bicarbonate or sulfite reduce the extent of the Mg2+ inhibition markedly. The activating anions may bind to CF1 in place of Pi near the ADP. Whether the inhibitory Mg2+ binds at catalytic or noncatalytic nucleotide binding sites or at another location is not known. The Mg2(+)- and ADP-induced inhibition appears to be a general property of F1 ATPases, which show considerable differences in affinity for ADP, Mg2+, and Pi. These differences may reflect physiological control functions.

Guanosine and formycin triphosphates bind at non-catalytic nucleotide binding sites of CF1 ATPase and inhibit ATP hydrolysis.

Guanosine triphosphate and formycin triphosphate (FTP) in the presence of excess Mg2+ can bind to empty non-catalytic sites of spinach chloroplast ATPase (CF1). This results in a greatly reduced capacity for ATP hydrolysis compared to the enzyme with non-catalytic sites filled with ATP. With two GTP bound at non-catalytic sites the inhibition is about 90%; with two FTP bound about 80% inhibition is obtained. Binding and release of the nucleotides from the non-catalytic sites are relatively slow processes. Exposure of CF1 with one or two empty non-catalytic sites to 5-10 microM FTP or GTP for 15 min suffices for about 50% of the maximum inhibition. Reactivation of CF1 after exposure to higher FTP or GTP concentrations requires long exposure to 2 microM EDTA. The findings show that, contrary to previous assumptions, GTP can bind tightly to non-catalytic sites of CF1. They suggest that the presence of adenine nucleotides at non-catalytic sites might be essential for high catalytic capacity of the F1 ATPases.

Tightly bound 2-azido-adenine nucleotides at catalytic and noncatalytic sites of the rat liver F1 ATPase label adjacent tryptic peptides of the beta subunit.

UV irradiation of rat liver F1 ATPase, previously exposed to Mg2+ and [beta, gamma-32P]-2-azido-ATP and separated from medium nucleotides, covalently modifies two tyrosine residues in adjacent tryptic peptides of the beta subunit. This results from the occupancy by 2-azido-ATP or 2-azido-ADP of two distinct types of nucleotide binding sites, the catalytic and noncatalytic sites. The two modified peptides are identical to the ones modified by 2-azido-adenine nucleotides in the beef heart F1 ATPase. Both catalytic and noncatalytic sites are labeled when the ATPase is exposed to [beta-32P]-2-azido-ADP in the presence or the absence of 5'-adenylyimidodiphosphate (AMP-PNP), showing that two distinct types of ADP binding sites are present on the liver enzyme. Similar incorporation of 2-azido-adenine nucleotides is obtained when membrane-bound rat liver F1 ATPase is incubated with Mg2+ and [beta, gamma-32P]-2-azido-ATP.