Should the 6-minute walk test be stopped if oxyhemoglobin saturation falls below 80%?

Publication date: Available online 18 August 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Sumbla Afzal, Angela T. Burge, Annemarie L. Lee, Janet Bondarenko, Anne E. Holland

Objective

To examine the occurrence of adverse events in patients undergoing assessment for pulmonary rehabilitation when a 6-minute walk test (6MWT) continues despite desaturation below 80%.

Design

Retrospective audit following REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement.

Setting

Large teaching hospital.

Participants

All patients assessed for pulmonary rehabilitation (September 2005 to January 2016).

Interventions

The standardized tests were conducted by experienced cardiorespiratory physiotherapists. Oxyhemoglobin saturation was monitored continuously using a pulse oximeter (lowest value used for analysis). Medical records were reviewed, and adverse events defined as tachycardia, bradycardia, chest pain or other sign/symptom necessitating cessation.

Main outcome measure

6MWT.

Results

Data from 672 walk tests were included (55% men, mean age 69 (standard deviation 11) years) with mean distance 369 (124) meters. The main diagnoses were chronic obstructive pulmonary disease (70%), interstitial lung disease (14%) and bronchiectasis (8%). Sixty individuals (11%) recorded desaturation below 80% without adverse events. Two adverse events were recorded during tests without desaturation; in one instance, chest pain with no evidence of cardiorespiratory compromise and in another, the patient stopped due to concern regarding blood sugar levels (11.5 mmol/L when tested). Independent predictors of desaturation to less than 80% were resting oxyhemoglobin saturation < 95% (odds ratio 3.82, 95% confidence interval 2.06 to 7.08) and a diagnosis of interstitial lung disease or pulmonary arterial hypertension (OR 5.24, 2.59 to 10.58).

Conclusions

This study found that desaturation to less than 80% during a 6MWT was not associated with adverse events in a large cohort of patients referred to pulmonary rehabilitation and assessed by experienced physiotherapists, suggesting that test cessation due to desaturation in stable patients may be unwarranted.

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Return-to-work barriers among manual workers after hand injuries: one-year follow-up cohort study

Publication date: Available online 18 August 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Batia S. Marom, Navah Z. Ratzon, Rafael S. Carel, Moshe Sharabi

Abstract

Objective

To determine time of return to work (TRTW) in relation to multivariable predictors among male manual workers after hand injury (HI) over a 12-month follow-up.

Design

A cohort study with baseline medical information, functional evaluation, and three-, six-, nine-, and 12-month follow-up telephone interviews.

Setting

Seven physical rehabilitation community occupational therapy clinics.

Participants

178 subjects with acute HI aged 22 to 65. Two participants were lost to follow-up.

Intervention

Not applicable.

Main Outcome Measure

The dependent variable was TRTW. The independent variables originated from four domains: personal factors, environmental factors, body function and structure, and activity limitation and participation restriction. The proportion of RTW at each time point was calculated. Multiple Cox regressions established a predictive model for TRTW.

Results

At the end of the study, 75.3% participants returned to work. The median TRTW was 94 days. In the final model, only compensation factors and education contributed significantly to overall RTW, but when separate analyses were performed, decreased level of self-efficacy, higher workplace demands, level of pain, level of emotional response to trauma, reduced physical capability of the hand, and higher level of disability were significantly associated with delayed TRTW.

Conclusions

TRTW was determined by the physical capability of the hand, pain, and psychosocial factors, but it was also affected by legal factors. Subjects who did not RTW during the first nine months are at risk for long-term disability. Developing treatment programs for those who are at risk for not RTW, taking into consideration these factors, is recommended.

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Quality of Life Trajectories among Stroke Survivors and the Related Changes in Caregiver Outcomes: A Growth Mixture Study

Publication date: Available online 18 August 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Gianluca Pucciarelli, Christopher S. Lee, Karen S. Lyons, Silvio Simeone, Rosaria Alvaro, Ercole Vellone

Abstract

Objectives

To identify the distinct quality of life (QoL) trajectories among stroke survivors, and to evaluate the associations with their caregivers' burden, anxiety, and depression.

Design

This was a longitudinal dyadic study.

Settings

Stroke survivors and their informal caregivers were enrolled upon discharge from several rehabilitation hospitals, and they were followed during this multisite longitudinal study.

Participants

The stroke survivors (n=405, mean age=70.7 years old) included older adult males (52.0%), most of whom (80.9%) had had ischemic strokes. The caregivers (n=244, mean age=52.7 years old) included mostly females (65.2%), most of whom were the survivors' children (50.0%) or spouses (36.1%).

Interventions

Not applicable

Main Outcome Measures

Latent growth mixture modeling was used to identify the distinct QoL trajectories among the stroke survivors over the course of 12 months of recovery. The longitudinal associations between the stroke survivor QoL trajectories and the caregivers' burden, anxiety, and depression were evaluated. A multinomial regression was then used to identify the predictors of the various survivor QoL trajectories.

Results

Three distinct survivor QoL trajectories were identified: "high and slightly improving QoL," "moderate and slightly worsening QoL," and "markedly improving QoL." The caregivers' burden, anxiety, and depression mirrored the survivors' QoL trajectories. In the multinomial models, an older survivor age, hemorrhagic stroke, lower education, and coexisting chronic obstructive pulmonary disease or thyroid disease were significantly associated with a "moderate and slightly worsening QoL" trajectory. Female gender and blindness were associated with a "markedly improving QoL" survivor trajectory.

Conclusions

A survivor's QoL trajectory after a stroke was associated with their caregiver's burden, anxiety, and depression. Those survivors belonging to the "moderate and slightly worsening QoL" trajectory and their caregivers, in particular, need special care, because they are at risk for the worst outcomes.

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Measuring the Reliability and Construct Validity of the Pediatric Evaluation of Disability Inventory – Computer Adaptive Test (PEDI-CAT) in Children with Cerebral Palsy

Publication date: Available online 18 August 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Benjamin J. Shore, Benjamin G. Allar, Patricia E. Miller, Travis H. Matheney, Brian D. Snyder, Maria Fragala Pinkham

Abstract

Objective

The purpose of this study was to (1) investigate the construct validity and (2) test-retest reliability of the Pediatric Evaluation of Disability Inventory – Computer Adaptive Test (PEDI-CAT) in children with cerebral palsy (CP).

Design

A prospective convenience cross-sectional sample

Setting

Multidisciplinary CP clinic in a tertiary level pediatric children's hospital

Participants

One hundred and one, English and Spanish speaking school aged children with a diagnosis of CP, stratified by Gross Motor Function Classification System level, who presented to our multidisciplinary clinic. Participants were excluded if they underwent recent surgery (<6months) or Botulinum Neurotoxin A injection (<3months). A subset of seventeen families participated in retest reliability.

Main Outcome Measures

Convergent and divergent validity were evaluated using Spearman's correlation analysis; test-retest reliability was assessed using intraclass correlation coefficients (ICC).

Results

Mean age was 12 years (SD=3.7). Convergent validity was established between Mobility (PEDI-CAT) and Functional Mobility Scale (FMS) (5m, r=0.85; 50m, r=0.84; 500m, r=0.76; p<0.001). In ambulant children, convergent validity was established between Daily Activities (PEDI-CAT versus Pediatric Quality of Life CP (PedsQL-CP) (r=0.85, p<0.001) and between Social/Cognitive (PEDI-CAT) and Speech and Communication (PedsQL-CP) (r=0.42; p<0.001). In non-ambulant children, convergent validity was established between Daily Activities (PEDI-CAT) and Personal Care [Caregiver's Priority and Child Health Index of Life with Disabilities – (CPCHILD^TM)] (r=0.44, p<0.001) and between Social/Cognitive (PEDI-CAT) and Communication (CPCHILD^TM) (r=0.64; p<0.001). A lack of correlation between Daily Activities, Social/Cognitive, and Responsibility (PEDI-CAT) and FMS and between the Mobility (PEDI-CAT) and Communication (PedsQL) domains confirmed divergent validity. Test-retest reliability was excellent for all domains of the PEDI-CAT (ICC=0.96-0.99).

Conclusions

The PEDI-CAT is an outcome measure which demonstrates strong construct validity and reliability in children with CP.

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Male gender and duration of anti-tuberculosis treatment are associated with hypocholesterolemia in adult pulmonary tuberculosis patients in Kampala, Uganda

Background: Patients with Pulmonary tuberculosis (PTB) and hypocholesterolemia have an altered immune function, delayed sputum conversion at two months and increased mortality. However, the assessment for dyslipidemias is not often done in our setting.
Methods: A cross-sectional study was conducted among adults at an urban TB clinic in Kampala, Uganda. We included different participants at diagnosis (0), 2, 5, 6 and 8 months of anti-TB treatment. Data was collected from a complete physical examination, a pre-tested structured questionnaire, six-hour fasting lipid profiles and random blood glucose levels.
Results: Of the 323 included participants, 63.5% (205/323) were males and the median age was 30 years, IQR (23-39). The prevalence of hypocholesterolemia was 43.65% (95% CI 38.3-49.2). The participants at diagnosis had the highest hypocholesterolemia prevalence, 57.3%, 95% CI (46.7-67.2); and lowest amongst those completing treatment at 6/8 months, 32.2%, 95% CI (21.6-45.2). Significant factors associated with hypocholesterolemia were: male gender (PR 1.52, 95% CI: 1.13-2.03), and duration of anti-TB treatment (0.88, 95% CI: 0.80-0.98).
Conclusion: Hypocholesterolemia is common among patients with PTB. The risk of hypocholesterolemia increases with being male and reduces with increased duration of treatment. There is a need for further research in lipid abnormalities in TB patients.

Keywords: Hypocholesterolemia, pulmonary tuberculosis, duration of anti-tuberculosis treatment, gender.

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Prevalence of rifampicin resistant tuberculosis and associated factors among presumptive tuberculosis patients in a secondary referral hospital in Lagos Nigeria

Background: Nigeria is one of the 30 high burden countries for drug resistant tuberculosis (DR-TB). This study assessed the prevalence and factors associated with rifampicin resistant tuberculosis (RR-TB) in a secondary referral hospital in Lagos State Nigeria.
Methods: A retrospective review of presumptive TB register of patients screened for Mycobacterium tuberculosis (MTB) and RR-TB using Xpert MTB/RIF assay at Mainland hospital between January 1 2012 and December 31 2016 was conducted.
Results: A total of 2497 clients were screened for MTB and RR-TB during the study period. The majority (51.4%) were between 25 – 44 years. Male: Female ratio was 1:0.8. Of the 2497 clients screened, MTB was detected in 942 (37.7%) out of which 220 (23.4%) had RR-TB. Age (AOR 1.8, 95%CI 1.3- 2.6, p = 0.001), symptomatic contact with DR-TB patients (AOR 3.3, 95%CI 2.1-5.1, p <0.001) and type of TB (AOR 2.9, 95% CI 1.7 – 5.0, <0.001) were associated with RR-TB after adjusting for age, gender, HIV status and symptomatic contacts with DR-TB patients.
Conclusion: The prevalence of RR-TB in new and previously treated TB patients was high in this study. Urgent steps are needed to avert an impending RR-TB epidemic

Keywords: Rifampicin resistance, tuberculosis, Xpert MTB/RIF, Lagos.

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Tribulus terrestris improves metronidazole-induced impaired fertility in the male mice

Introduction: Fruit extract of Tribulus terrestris (TT) bears aphrodisiac and antioxidative properties. Antimicrobial drug, metronidazole (MTZ) impairs the spermatogenic activity and fertility in males.
Objective: Validation of the use of fruit extract of TT as a supplement against MTZ-induced fertility impairment in males.

Methods: Adult Swiss strain male mice were administered with 500mg/kgBW/day of MTZ for 28 days. Low (100mg/kgBW/day) and high (200mg/kgBW/day) doses of TT were administered simultaneously with MTZ (500mg/kgBW/day) for same duration. All males were cohabited with virgin proestrus females. Vaginal plug formation was observed to calculate the libido index. Cohabited females were sacrificed on fifteenth day of gestation to dissect out the ovaries and uteri. Fertility index, quantal pregnancy, pre-implantation and post-implantation losses were calculated. 

Results: MTZ-treated males showed unaltered mating ability, however, the females impregnated by such males exhibited marked alterations in the fertility index, quantal pregnancy and pre- and post-implantation losses. Supplementation with low dose of TT failed to restore such reproductive toxicities exhibited by administration of MTZ. However, the altered reproductive toxicities were reinstated to control values following supplementation with high dose of TT.
Conclusion: The fruit extract of TT may emerge as an effective herbal remedy, correcting the drug-induced fertility impairments in males.

Keywords: Female mice, fertility, male mice, metronidazole, Tribulus terrestris.

 

 

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Effects of aqueous extract of Moringa oleifera seed on cadmium-induced reproductive toxicity in male Wistar rats

Bacground: Moringa oleifera seeds have been reported to increase sexual activity of male rats but its mechanism of action remains unknown.

Objective: Cadmium is a heavy metal that induces reproductive toxicity. To elucidate its possible mechanisms of action, the effects of aqueous extract of Moringa seeds (AEMS) on Cadmium-induced reproductive damage were investigated.
Methods: Thirty male rats (180-200g, n=5) were grouped as follows: Control, Cadmium (2mg/kg), AEMS (100 and 500mg/kg), Cadmium+100mg/kg AEMS and Cadmium+500mg/kg AEMS. Single intraperitoneal dose of Cadmium was administered while AEMS was given daily (p.o) for 6 weeks and thereafter sacrificed by cervical dislocation. Sperm variables were examined microscopically while serum was analysed for sex hormones and antioxidants, testicular and epididymal total protein from tissue homogenate. Data were analysed using Students t-test and ANOVA.
Results: Cadmium caused significant decrease in sperm variables. The AEMS decreased sperm motility, count and testosterone. These declines were dose dependent. Total testicular protein was significantly lowered by AEMS but total epididymal protein was not affected. Serum catalase and SOD was reduced by AEMS while MDA increased.
Conclusion: Moringa seeds may exhibit male reproductive toxicity, as observed from its deleterious effect on androgen and sperm variables. It failed to prevent cadmium-induced alteration in reproductive variables and serum antioxidants.

Keywords: Aqueous extract, Moringa oleifera seed, cadmium-induced reproductive toxicity, male Wistar rats.

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Cystic fibrosis in Tunisian children: a review of 32 children

Background: Cystic fibrosis is rare in Tunisia.Its diagnosis requires experienced specialists. Its prognosis is poor in developing countries.
Objectives: To study the epidemiologic, clinical, genetic features and the therapeutic challenges of cystic fibrosis in Tunisian children.
Methods: Covering a period of 21 years, this retrospective study included all patients with a definite diagnosis of cystic fibrosis from the Pediatrics Department B of The Children's Hospital of Tunis.
Results: Data from 32 children (14 boys and 18 girls) were collected. The diagnosis was made during the first year of life in 28 cases. Meconium ileus was found in 5 cases, respiratory manifestations in 22 cases, chronic diarrhea in 19 cases, faltering growth in 17 cases and a pseudo Barter syndrome in 2 cases. The sweat chloride test was positive in all cases. The most frequent mutation was F508del (56% of cases). Respiratory complications marked the outcome. Among our 32 patients, 15 patients (50%) died at an average age of 5 years and 3 months, mainly due to respiratory failure. The mean age of the surviving patients was 5 years.
Conclusion: Cystic fibrosis prognosis is poor in our series compared to developed countries due to the longer diagnostic delay and the limited therapeutic options.

Keywords: Cystic fibrosis, children, Tunisia.

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A study on visual, audio and tactile reaction time among medical students at Kampala International University in Uganda

Background: Reaction time (RT) is an indicator of neural activity, however, its variation due to visual (VRT), audio (ART) and tactile (TRT) in African medical students has not been investigated. The aim of the study was to determine relationships between VRT, ART and TRT amongst medical students in Uganda.
Materials and methods: This was a cross sectional study, the body mass index (BMI) and RT (i.e. VRT, ART and TRT) were determined using weighing scale with standiometer and the catch a ruler experiment respectively. A questionnaire was administered to collect information on participant's lifestyle patterns and analysis was done using SPSS Version 20.
Results: The mean (± SEM) VRT, ART and TRT in the study were found to be 0.148 ± 0.002s, 0.141 ± 0.002s and 0.139 ± 0.003s respectively. A strong correlation between TRT and ART was found to exist in the youthful Ugandan medical student's population. Furthermore, significant differences in ART and VRT were observed with sex, although these were absent amongst preclinical and clinical students, showing the importance of sex in RT.
Conclusion: The low VRT and ART in Ugandan medical students is indicative of a healthy somatosensory connectivity, thus of academic importance.

Keywords: Reaction time, cognitive performance, neural health, medical education.

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Family physicians' utility of social media: a survey comparison among family medicine residents and physicians

Introduction: Social media has become ubiquitous and has brought a dramatic change in health services. Little is known about its use by family physicians and residents for personal or professional purpose. The aim of the current study was to evaluate the utility of social media among family medicine residents and consultants.
Methods: The collection of data was through the use of a five part questionnaire developed by researchers. The questionnaire was delivered to 70 physicians and 100 residents, out of which 132questionnaires were completed, representing a 78 percent response rate.
Results: Our findings demonstrate that there was an overall high use of social media. Females used social media more for general education and professional purposes. Men, by contrast, used it more frequently for personal purposes. The participants in this study appeared to consider social media as having several useful dimensions, such as: enabling them to accomplish job tasks, improve job performance, productivity and more effective patient care when using social media.
Conclusions: To date, limited studies have compared social media use among family physicians and residents. This study may serve as an initial step for future studies explaining the pattern of use among physicians.

Keywords: Social media, family physicians, learning, pattern of use, attitudes and gender differences.

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A randomized control trial comparing train of four ratio > 0.9 to clinical assessment of return of neuromuscular function before endotracheal extubation on critical respiratory events in adult patients undergoing elective surgery at a tertiary hospital in

Background: There is increasing evidence that the incidence of postoperative residual paresis after using neuromuscular blockers ranges from 24 to 50% in post anaesthesia care unit (PACU) and is associated with postoperative complications such as critical respiratory events as evidenced by hypoxia, hypoventilation and upper airway obstruction. Quantitative neuromuscular monitoring (such as the assessment of Train of four (TOF) ratio) and reversal of neuromuscular blockers has been shown to reduce postoperative residual paresis. There are very few outcome studies on effect of residual paresis in PACU. There is a paucity of published randomized controlled trials investigating whether using a TOF ratio ≥0.9 before endotracheal extubation compared to clinical assessment of return of neuromuscular function reduces the incidence of critical respiratory events in PACU.
Objective: To determine whether using TOF ratio ≥ 0.9 compared to clinical assessment of return of neuromuscular function before endotracheal extubation reduces the incidence of critical respiratory events in PACU
Methods: Onehundred sixty eight adult patients in ASA physical status I and II requiring general anaesthesia for elective surgery with cisatracurium as the muscle relaxant were randomized into 2 groups of 84 each. Group 1 were patients who required a TOF ratio of ≥0.9 before extubation. Group 2 patients were extubated based on clinical assessment of return of adequate neuromuscular function by the anaesthetist as is the standard of practice at the Aga Khan University hospital Nairobi. General anaesthesia was standardized in both groups. Both the investigators and patients were blinded during the study. Once the patient was transferred to PACU, oxygen saturation (SP02), respiratory rate and any signs of upper airway obstruction as demonstrated by stridor, laryngospasms or requirement of any airway manipulation was recorded for the first 30 minutes. Duration of anaesthesia and surgery was also recorded. Patient demographics were recorded and analyzed.
Results: There was no statistical difference between the 2 groups in terms of patient demographics, duration of surgery and anaesthesia and duration since last muscle relaxant was given. In terms of hypoxia on arrival in PACU, the incidence of mild hypoxia (SPO2 90-93%) was 11% in clinical assessment groupversus 5% in TOF group P-value 0.149 while severe hypoxia (SPO2 <90%) was 19% versus 10% P-value 0.078. During the first 30 minutes in PACU, the incidence of mild hypoxia (SPO2 90-93%) was statistically significant between the 2 groups (12% in clinical assessment group versus 1% in TOF group, P-value 0.005) while severe hypoxia (SPO2 <90%) was 7% versus 5%, P-value 0.373. The incidence of upper airway obstruction was statistically significant between the two groups (45% in clinical assessment group versus 14% in TOF group P-value<0.0001 for patients requiring airway maneuver, 21% versus 2% P-value <0.0001 for those who required tactile stimulation and 31% versus 12% were snoring, P-value 0.003. Logistic regression analysis revealed TOF group was less likely associated with mild hypoxia (OR 0.09 95% CI 0.01-0.71 P-value 0.023), tactile stimulation (OR 0.09 95% CI 0.02-0.40 P-value 0.002), airway maneuver (OR 0.20 95% CI 0.10-0.43 P-value <0.001) and snoring (OR 0.30 95% CI 0.13-0.68 P-value 0.04).
Conclusion: Among this population, there is a lower incidence of critical respiratory events in PACU with the use of neuromuscular monitoring using TOF ratio ≥0.9 to assess neuromuscular function before endotracheal extubation compared with the use of clinical assessment methods.

Keywords: Randomized control trial, neuromuscular function, elective surgery, Nairobi.

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MR imaging of intracranial solitary fibrous tumor: a retrospective study of 7 cases

Objective: To investigate the MR imaging diagnostic features of intracranial solitary fibrous tumors (ISFTs).
Materials and methods: Seven patients (mean age of 52.9 years; M:F=3:4) with histopathologically proven ISFTs were identified at our institute. Clinical presentations and pathological features were reviewed. MR Imaging findings including signal intensity, gadopentetate dimeglumine enhanced pattern, and diffusion-weighted imaging (DWI) characterization of the tumors were retrospectively evaluated.
Results: Six tumors showed a multi-lobular contour. Five tumors showed heterogeneous signal intensity, and two tumors showed homogeneous signal intensity on T1WI. Low signal intensity linear, curved or interlacing lines were observed within the tumors in all seven cases. Seven tumors demonstrated moderate or strong enhancement, six showed heterogeneous enhancement, and one homogenous enhancement. All tumors showed heterogeneous signal intensity on DWI.A ring–like high signal intensity band distributed around within the tumor was noted in six cases on DWI.
Conclusion: Diagnostic evidence for ISFT on MR image includes heterogeneous signal intensity, intense enhancement of T2 signal intensity, low signal intensity lines within the tumor, heterogeneous signal intensity on DWI and a ring-like band around the tumor on DWI.

Keywords: Intracranial Solitary Fibrous Tumor, Magnetic resonance imaging, Diffusion-weighted Imaging.

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AGREE-II Appraisal of a clinical algorithm for hypotonia assessment

Objective: The objective of this study was to systematically appraise the quality of an evidenced-based clinical algorithm for the clinical assessment of hypotonia in children.
Design: The Appraisal of Guidelines for Research and Evaluation (AGREE) II tool with 23 items and six domains was used. The study was located in South Africa. Ten appraisers, who were recruited based on specific selection criteria, completed the assessment.
Results: Nine appraisers recommended the EBCA without any modification. Scope and purpose (94%), stakeholder involvement (91%) and editorial independence (99%) were rated the highest with the lower scoring domains being clarity of presentation (85%) and applicability (86%) due to clarity required in areas of resource implications and auditing and monitoring criteria. Inter-rater reliability was strong (ICC 0.7) amongst the appraisers in this study.
Conclusion: This is the first independent assessment of the methodological rigour and transparency of a clinical algorithm using the AGREE-II instrument. Determining the quality of the EBCA for practice is essential as this would ultimately aid clinicians towards more accurate clinical assessment of hypotonia which would inevitably impact outcomes and management of the child presenting with this symptom. Whilst the AGREE-II provided initial feedback on the methodological rigour of development, understanding that the AGREE-II instrument evaluates the guideline development process and not the content is also essential in order to consider the next stage which would be to consider clinicians feedback on the clinical utility of this EBCA.

Keywords: AGREE-II; clinical algorithm; hypotonia, low muscle tone; paediatrics.

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Neuroleptic malignant syndrome in a young adult female at the university of Benin Teaching Hospital: a case report

Background: Neuroleptic malignant syndrome is a rare but life-threatening idiosyncratic complication following the use of antipsychotic agents, anaesthesia and surgery. It is characterized by hyperthermia, muscle rigidity, autonomic disturbances and mental state alterations.
Case: A 31 year old female weighing 60kg received a depot preparation of Fluphenazine on account of depression with psychotic features observed two days prior to elective Cholecystectomy under general anaesthesia. Surgery and anaesthesia were essentially uneventful. Forty eight hours post-operatively, the patient developed features suggestive of neuroleptic malignant syndrome complicated by aspiration pneumonitis. This necessitated her admission into the intensive care unit. She had prolonged stay in the intensive care unit, where she was mechanically ventilated, developed deep venous thrombosis of the left upper limb and required tracheostomy on account of prolonged endotracheal intubation. Patient recovered fully following bromocriptine and dantrolene therapy. She was discharged home after 60 days on admission and has remained in good health.
Conclusion: Though rare, neuroleptic malignant syndrome can occur in young adult females following use of antipsychotics, anaesthesia and surgery. Its clinical course can be prolonged and distressing with the use of depot preparations. Early diagnosis and prompt supportive measures are essential to reduce morbidity and mortality.

Keywords: Neuroleptic malignant syndrome, adult female, University of Benin Teaching Hospital.

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Substance abuse among students in selected secondary schools of an urban community of Oyo-state, South West Nigeria: implication for policy action

Background: Substance abuse among youths is fast becoming a global Public Health concern.
Objectives: This study assessed the prevalence and factors associated with substance abuse in selected public schools in Ogbomoso, South-West Nigeria.
Methods: Cross-sectional study design and multi-stage sampling method were utilized among 249 study participants who gave informed consent/assent. Data were collected using facilitated, self-administered questionnaire.Descriptive and inferential statistics using the Chi-Square test were carried out at p<0.05.
Results: The mean age of our respondents was 16.3±2SD; 40.0% of them had positive attitude to substance abuse while 21.7% had ever consumed alcoholic drinks. In all, 31(26.3%) of the respondents satisfied the criteria used in defining substance abuse.Tramadol was the most commonly abused substance apart from alcohol; reported by 39.0% of the substance abusers. Most (35.5%) of the substance abusers did so believing it could enhance their academic performance. The proportion of respondents who were substance abusers was significantly higher among students who had not received any formal lectures on the subject at school compared to those who had.(47.5% vs 29.7% ;p=0.023).
Conclusion: Our findings underscore an urgent need to intensify awareness against substance abuse among secondary school students in Nigeria.

Keywords: Substance abuse, youth, adolescents, attitude, secondary schools, Nigeria.

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Effect of tramadol addiction alone and its co-abuse with cannabis on urinary excretion of Copper, Zinc, and Calcium among Egyptian addicts

Background: The use of illicit drugs has become a worldwide health problem. Substances with the potential to be abused may have direct or indirect effects on physiologic mechanisms that lead to organ system dysfunction and diseases.
Objective: The present study aims to investigate the structural and reabsorption integrity of the nephron among Egyptian addicts of tramadol alone and coabused with cannabis.
Methods: Sixty-five males were included in the study, they were classified into control group (G1=19), tramadol addicts group (G2=18), and tramadol coabused with cannabis addicts group (G3=28). Parameters investigated for structural integrity were urinary levels ofleucineaminopeptidase and N-acetyl-β-D-glucosaminidase, and urinary parameters for reabsorption integrity were levels of copper and zinc as well as calcium, also urinary creatinine was measured. In addition, urinary levels of tramadol and tetrahydrocannabinol were estimated.
Results: Among the two addicted groups, all measured parameters were not significantly different in comparison with the control group except for urinary calcium excretion which was found to be significantly increased among the two addicted groups.
Conclusion: Both tramadol addiction alone or coabused with cannabis causes increased urinary excretion of calcium, indicating reabsorption dysfunction of calcium without affecting structural integrity along the nephron.

Keywords: Enzymuria, copper, zinc, calcium, reabsorption impairment, tubular structural integrity.

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Under nutrition and associated factors among school adolescents in Dangila Town, Northwest Ethiopia: a cross sectional study

Background: Under nutrition in adolescents is an important determinant of health outcomes. Yet, adolescents are not usually part of health and nutrition surveys. Therefore, this research was conducted to assess factors associated with under nutrition among school adolescents.
Method: A cross-sectional study was conducted among 424 school adolescents from November 1-15, 2015. Simple random sampling was used to select the study participants. Data were collected using structured questionnaire and analyzed by SPSS version 20 software. Both bivariate and multivariable logistic regression analyses were carried out to identify predictors of under nutrition. Furthermore, anthropometric data were calculated using Anthro-plus software.
Result: The prevalence of stunting and thinness were 24.8 % and 7.1 %, respectively. Male gender [AOR=3.2, 95 % CI: (1.7, 5.8)], infrequent food intake [AOR=4.6, 95% CI: (2.6, 8.0)], unavailability of latrine [AOR=2.7, 95 % CI: (1.2, 6.0)], and poor hand washing practice [AOR=3.9, 95 % CI: (1.9, 8.1)] were independent predictors of stunting. Factors associated with thinness were being male [AOR=11.5, 95% CI: (3.3, 39.5)], illness in the last two weeks [AOR=2.9, 95 % CI: (1.2, 7.0)], and having more than five family members [AOR=3.6, 95% CI: (1.3, 9.4)].
Conclusion: The prevalence of under nutrition was high in this study. Infrequent food intake, unavailability of a latrine, poor hand washing practice, and large family members were the factors associated with under nutrition. There is need to implement nutrition education to school adolescents by giving emphasis on environmental and personal hygiene.

Keywords: Adolescent, stunting, thinness.

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Nutrition knowledge, dietary patterns and anthropometric indices of older persons in four peri-urban communities in Ga West municipality, Ghana

Background: Older adults are vulnerable to malnutrition due to sociologic, physiologic and anatomical effects of ageing.
Objective: To investigate the influence of nutrition knowledge and dietary patterns on nutritional status of community-dwelling ambulatory older adults.
Methods: This cross-sectional survey involved 120 elderly aged 60-70 years purposively selected from four peri-urban communities in Ga West municipality, Ghana. Nutrition knowledge was assessed using a structured questionnaire and dietary intakes obtained using a standardized food frequency questionnaire. BMI from weight/height measurements was proxy for nutritional status. Data was analyzed descriptively in SPSS. Associations were tested using correlation analyses (-1<r<+1).
Results: 28% had adequate knowledge on geriatric nutrition. Dietary patterns were mostly fair (40%) or poor (53%). Bloating (25%), constipation (18%), appetite loss (12%) and chewing difficulties (11%) affected intakes. Underweight was 10% while 21.7% were overweight or obese (16.6%). Positive insignificant corrections existed between knowledge and nutritional status (r=0.261) and with diet quality (r=0.415). However, strong significant (p=0.027) positive correlation (r=0.699) existed between diet quality and nutritional status.
Conclusion: Nutrition knowledge was adequate but dietary intake was poor and a quarter were malnourished. The associations reaffirm that supporting the elderly to make healthy dietary choices and ensuring household food security is crucial to preventing malnutrition.

Keywords: Dietary knowledge, food diversity, body mass index, elderly, geriatric nutrition.

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Vitamin A deficiency among under-five Nigerian children with diarrhoea

Background: Vitamin A deficiency (VAD) and diarrhoea are still important contributors to childhood deaths in Africa, and vitamin A deficient children are at increased risk as well as severity of diarrhoea.
Objectives:To determine the prevalence of VAD and identify the associated factors among children with diarrhoea.
Methods: The study was a hospital-based cross-sectional descriptive study. Consecutive children with diarrhoea were recruited, provided they met the inclusion criteria. Serum retinol levels were determined by high performance liquid chromatography (HPLC) in one hundred and seventy under-five children who presented with diarrhoea at the Wesley Guild Hospital, Ilesa, Nigeria.
Results: The serum retinol levels of the children ranged from 0.29 – 2.35 µmol/L with a mean ± SD of 1.07 ± 0.42 µmol/L. Twenty seven (15.9%) were vitamin A deficient with three (1.8%) of these having severe VAD. Wasting was significantly associated with a higher prevalence of VAD [p = 0.023, OR (95% CI) = 3.08 (1.21 - 7.79)]. A significantly greater proportion of the subjects who had VAD were hospitalized, compared with the non-deficient ones [p = 0.001, OR (95% CI) = 4.40 (1.82 - 10.66)]. The only subject who died was vitamin A deficient.
Conclusion: Wasting and hospitalization are factors that may indicate the presence of VAD in a child with diarrhoea. Vitamin A supplements should therefore be given, as part of the treatment for diarrhoea, to children who have wasting, especially when they require hospitalization.

Keywords: Vitamin A deficiency, Nigerian children, diarrhoea.

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Status of thiocyanate levels in the serum and saliva of non-smokers, ex-smokers and smokers

Background: Use of tobacco is often implicated in the development of oral diseases. Questionable accuracy of the traditional questionnaires to assess cigarette exposure necessitates the use of biomarkers like thiocyanate which provide a definitive quantitative measure.
Objective: To assess the rise in the level of thiocyanate for measurement of smoking behaviour in adults.
Materials and methods: Serum and salivary thiocyanate levels were estimated in 20 non-smokers, 20 ex-smokers and 40 smokers. Smokers were divided into two groups based on the presence or absence of oral mucosal lesions.
Results: The mean serum and salivary thiocyanate levels were increased significantly in smokers when compared to non-smokers and ex-smokers. The levels were not significantly different between ex-smokers and non-smokers and between smokers with tobacco related oral mucosal lesions and those without. Statistically significant correlation was seen between the serum and salivary levels of thiocyanate.
Conclusion: This study highlights the high level of thiocyanate in the serum and saliva of smokers when compared to non-smokers and ex-smokers. Significant increase in thiocyanate level was also seen in saliva. Hence it can be stated that saliva can be used as a reliable, non-invasive tool to assess smoking behaviour in the population and its changes over time.

Keywords: Thiocyanate, tobacco, smoking, cancer, pre-cancer.

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Association of serum asymmetric dimethyl-arginine and troponin I levels as a risk of myocardial infarction in thalassemia

Background: The current study evaluated level of serum asymmetric dimethylarginine (ADMA) and its association to cardiac biomarkers in thalassemia patients for early diagnosis of abnormality in myocardial infarction.
Subjects and methods: This study was conducted on 80 subjects divided into four groups each with 20 subjects. Group I: Control: healthy subjects. Group II: Myocardial infarction: Patients with elevated serum troponin T. Group III: thalassemia patients. Group IV: thalassemia with myocardial infarction patients: Included 20 thalassemia patients with Myocardial infarction. Serum samples were subjected for assay of creatine kinase (CK:MB), Lactate dehydrogenase, troponin I ,ADMA, Serum MDA level was determined.
Results: Data obtained showed that serum CKMB, LDH1, AST, Troponin T and ADMA levels were significant elevated in MI with or without Thalassemia compared with control groups. Serum MDA was statistically significantly elevated in MI with or without Thalassemia compared with control groups. The serum level of troponin T showed an area under curve (AUC) of 0.92 ,(sensitivity 91.0 % and specificity, 88%). Also, the ADMA supported the diagnostic profile, showing an AUC of 0.85 with (sensitivity, 92.0%; specificity, 91,9%).
Conclusion: Serum ADMA is sensitive marker for incidence of MI in thalassemia patients.

Keywords: CKMB, LDH1, AST, Troponin T, asymmetric dimethylarginie, Thalassemia.

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Thyroid profile and LDH Isoenzymes as prognostic biomarkers for diabetic and/or obese subjects

Background: This study aimed to evaluate the levels of thyroid hormones and lactate dehydrogenase (LDH) isoenzymes in obese and/or diabetic patients.
Subjects and methods: Forty male subjects categorized into four equal groups; group 1: Non obese control subjects, group 2: Subjects suffering from type 2 diabetes mellitus (T2DM), group 3: Obese subjects (BMI ≥ 30 kg/m2) and group 4: Subjects thatwere obese and had type 2 diabetes mellitus (T2DM). Liver, kidney, lipid, thyroid hormones, total LDH and LDH isoenzymes levels were determined.
Results: There was a significant increase of TSH level (p<0.001) in diabetic group as compared with control group and a highly significant increase of TSH was obtained in obese and obese diabetic groups versus control and diabetic patients. LDH 2 was also highly significantly decreased in obese and obese diabetic groups versus diabetic patients. Percentage of LDH 4 was significantly decreased in both diabetic and obese groups and not significantly changed in obese diabetic patients as compared with the control group. LDH 5 percentage showed very highly significant decrease in diabetic, obese and highly significant decrease in obese diabetic groups when compared with control subjects while it was not significantly changed in obese and obese diabetic groups as compared with diabetic patients.
Conclusion: LDH isozymes can be used as valuable diagnostic markers for metabolic syndrome. This may help to explore the metabolic changes associated with obesity and diabetes complication and following up the complication of these abnormalities.

Keywords: Thyroid profile, lactate dehydrogenase, obesity, diabetes.

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Knowledge, attitude and practice towards cervical cancer among women in Finote Selam city administration, West Gojjam Zone, Amhara Region, North West Ethiopia, 2017

Introduction: Cancer of the cervix is the leading cause of cancer-related death among women, especially in developing countries affecting women at a time of life when they are critical to social and economic stability.
Method: The study was conducted at Finote Selam City Administration from February 01 to March 01, 2017 using a community-based cross-sectional study design. The representative sample size was selected using multistage sampling technique. The data were collected using an interviewer-administered questionnaire adapted from the previous study. Data were entered using EpiData Version 3.1 statistical software and analyzed using SPSS version 20 statistical package.
Result: One hundred seventy (23.1%) were knowledgeable about cervical cancer whereas 63% of participants had a negative attitude and only 7.3% had ever screened for the disease. Logistic regression analysis showed that age, marital status, religion, experienced sexual intercourse and age at 1st sexual intercourse were found to be significantly associated with the knowledge of cancer of the cervix.
Conclusion: Ministry of health in collaboration with other concerned bodies should design a strategy to give education about cervical cancer including information on risk factors, signs and symptoms; and availability of screening should be provided for women and as well as for the public.

Keywords: Cervical cancer, screening, Finote Selam, North West Ethiopia.

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Pancreatic cancer: French Clinical Practice Guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC)

This document is a summary of the French Intergroup guidelines regarding the management of pancreatic adenocarcinoma (PA), updated in July 2018.

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Pitfalls in the reporting OF upper endoscopy features in cirrhotic patients

Upper endoscopy is the main tool for the accurate assessment of the risk of bleeding in cirrhotic patients.

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Endoscopic findings and esophageal cancer incidence among Fanconi Anemia patients participating in an endoscopic surveillance program

WHAT IS CURRENT KNOWLEDGEWHAT IS NEW HERE

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Examining Childhood Obesity From Infancy: The Relationship Between Tummy Time, Infant BMI-z, Weight Gain, and Motor Development—An Exploratory Study

This exploratory study investigated the infant time spent in tummy time (TT) in relation to body mass index z score (BMI-z), weight gain, and motor development in infants from birth to 4 months.

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Pancreatic cancer: French Clinical Practice Guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC)

This document is a summary of the French Intergroup guidelines regarding the management of pancreatic adenocarcinoma (PA), updated in July 2018.

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Pitfalls in the reporting OF upper endoscopy features in cirrhotic patients

Upper endoscopy is the main tool for the accurate assessment of the risk of bleeding in cirrhotic patients.

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Endoscopic findings and esophageal cancer incidence among Fanconi Anemia patients participating in an endoscopic surveillance program

WHAT IS CURRENT KNOWLEDGEWHAT IS NEW HERE

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CRISPR/Cas9-introduced single and multiple mutagenesis in strawberry

Publication date: Available online 18 August 2018

Source: Journal of Genetics and Genomics

Author(s): Sinian Xing, Meiru Jia, Lingzhi Wei, Wenwen Mao, Usman Ali Abbasi, Yaoyao Zhao, Yating Chen, Minglin Cao, Kai Zhang, Zhengrong Dai, Zhechao Dou, Wensuo Jia, Bingbing Li

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Gender effects on auditory P300: A systematic review

Publication date: Available online 18 August 2018

Source: International Journal of Psychophysiology

Author(s): Sigita Melynyte, Grace Y. Wang, Inga Griskova-Bulanova

Abstract

The evidence suggests that gender-related effects could influence the electrophysiological P300 parameters and stand as an additional source of variation for both clinical and non-clinical subjects. The aim of this paper is to characterize gender-related differences in P300 potential as elicited with simple auditory paradigms. This knowledge (1) is important for the practical assessment of P300 potential in normal and clinical populations, and (2) can provide insight into the understanding of gender differences in pathophysiology, particularly those with differential risk or prevalence in males and females. With this review, a limited number of studies encounter possible gender effects on parameters of auditory P300, and the study findings need to be read with caution due to their methodological limitations. Nevertheless, evidence supports that the P300 amplitude could be significantly modulated by gender, with greater amplitude in females relative to males. Noteworthy, gender has a minimal effect on the P300 latency, and it is often comparable between males and females. Furthermore, the effect of gender on P300 could be modulated by hormonal background, anatomy and some methodological aspects.

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Characteristics of artificial radionuclides in sedimentary soil cores from a volcanic crater lake

Publication date: December 2018

Source: Journal of Environmental Radioactivity, Volume 192

Author(s): Seong A. Yim, Jung-Seok Chae, Jong-In Byun, Suk-Hyung Ko

Abstract

The distributions of ¹³⁷Cs, ²³⁷Np, and ^239+240Pu activity concentrations in sedimentary soil cores of the volcanic crater-lake have been studied. The ²⁴⁰Pu/²³⁹Pu atom ratios measured by MC-ICP-MS and mutual activity ratios were examined. These results were used to evaluate the sedimentation characteristics of the crater-lake (Baengnokdam of Mt. Halla, Korea). The ¹³⁷Cs, ²³⁷Np, and ^239+240Pu activity concentrations showed similar distribution patterns and one maximum peak was observed in each sediment core, except at St.10. For all sediment cores, the activity concentrations were in the range 1.03 × 10⁰–1.92 × 10² Bq·kg⁻¹ dw for ¹³⁷Cs, 7.56 × 10⁻³ – 7.15 × 10⁰ mBq·kg⁻¹ dw for ²³⁷Np, and 5.20 × 10⁻³ – 5.13 × 10⁰ Bq·kg⁻¹ dw for ^239+240Pu, respectively. The averaged ²⁴⁰Pu/²³⁹Pu atomic ratio (0.159) was slightly less than the global fallout ratio (0.176). The averaged inventories were estimated to be 9.21 × 10³±5.34 × 10³ Bq·m⁻² for ¹³⁷Cs, 2.27 × 10²±1.58 × 10² Bq·m⁻² for ^239+240Pu, and 3.22 × 10⁻¹±1.78 × 10⁻¹ Bq·m⁻² for ²³⁷Np. The averaged ^239+240Pu/¹³⁷Cs and ²³⁷Np/^239+240Pu activity ratios were 2.21 × 10⁻² and 2.21 × 10⁻³, respectively.

The mean sedimentation rates calculated using ^239+240Pu activity concentrations at the central area (St.30 – St.45) and at all stations (St.5 – St.75) were estimated to be 0.844 cm yr⁻¹, and 0.767 cm yr⁻¹, respectively. In addition, the sedimentation rates calculated using ²¹⁰Pb and ²²⁶Ra were 0.856 cm yr⁻¹ at depths of 0–35 cm and 0.204 cm yr⁻¹ at depths of 35–55 cm. These results imply that the sedimentation in Baengnokdam was relatively slow (0.204 cm yr⁻¹) until about 44 years ago and then became faster (0.856 cm yr⁻¹) to the present. The excess ²¹⁰Pb dating is consistent with the sedimentation rate calculated from the vertical ^239+240Pu profile.

Graphical abstract

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Heart rate and pulmonary oxygen uptake response in professional badminton players: comparison between on-court game simulation and laboratory exercise testing

Abstract

Purpose

Badminton is characterized by bouts of high intensity interspersed by short recovery periods. Aerobic assessment via indirect calorimetry is impractical on court because of the encumbrance of portable metabolic devices. When the relationship between heart rate (HR) and pulmonary oxygen uptake \(\left( _}} \right)\) \(\left( \;{\text{vs}}\;__2}}}} \right)\) is linear, HR monitoring can provide an indirect estimation of metabolic demands on court. However, owing to the intermittent nature of badminton, the \({\text{HR}}\;{\text{vs}}\;{\dot {V}__2}}}\) relationship will differ from that obtained in the laboratory, making its use on court questionable. The aims of this study were to (i) assess cardiorespiratory and metabolic responses during on-court badminton rally simulations at different intensities and (ii) compare \({\text{HR}}\;{\text{vs}}\;{\dot {V}__2}}}\) relationships obtained from laboratory and on-court measurements.

Methods

The study sample was seven professional badminton players (age 16.9 ± 2.1 years; body mass 62.8 ± 9.2 kg; stature 1.71 ± 0.09 m). \({\dot {V}__2}}},\) HR, and other respiratory and metabolic parameters were assessed in the laboratory with an incremental intermittent Astrand-type test (IIAT) and on court during rally simulations at three different intensities.

Results

Cardiorespiratory parameters measured during the rallies reached 95% of maximal IIAT values. The \({\text{HR}}\;{\text{vs}}\;{\dot {V}__2}}}\) slope and intercept differed in the on-court and the IIAT conditions (P = 0.012 and P = 0.008, respectively).

Conclusions

The difference in \({\text{HR}}\;{\text{vs}}\;{\dot {V}__2}}}\) regression lines between the IIAT and the on-court condition indicates that HR monitoring may not provide accurate data on the aerobic demands of specific on-court badminton tasks. HR monitoring should be preceded by an indirect calorimetry test on court to assess aerobic demands more precisely.

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Editorial Board

Publication date: September 2018

Source: Gene Expression Patterns, Volume 29

Author(s):

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South Korea: in the midst of a privacy reform centered on data sharing

Abstract

With rapid developments in genomic and digital technologies, genomic data sharing has become a key issue for the achievement of precision medicine in South Korea. The legal and administrative framework for data sharing and protection in this country is currently under intense scrutiny from national and international stakeholders. Policymakers are assessing the relevance of specific restrictions in national laws and guidelines for better alignment with international approaches. This manuscript will consider key issues in international genome data sharing in South Korea, including consent, privacy, security measures, compatible adequacy and oversight, and map out an approach to genomic data sharing that recognizes the importance of patient engagement and responsible use of data in South Korea.

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Effects of endurance training on neuromuscular fatigue in healthy active men. Part I: Strength loss and muscle fatigue

Abstract

Purpose

The adaptations induced by endurance training on the neuromuscular function remain under investigation and, for methodological reasons, unclear. This study investigates the effects of cycling training on neuromuscular fatigue and its peripheral contribution measured during and immediately after cycling exercise.

Methods

Fourteen healthy men performed a fatigue test before a 9-week cycling program (PRE) and two tests after training: at the same absolute power output as PRE (POST_ABS) and based on the post-training maximal aerobic power (POST_REL). Throughout the tests and at exhaustion (EXH), maximal voluntary contraction (MVC) and peripheral fatigue were assessed in the quadriceps muscle by electrical nerve stimulation [single twitch (Pt); high-frequency doublet (Db₁₀₀) and low-to-high-frequency ratio (Db_10:100)].

Results

Time to EXH was longer in POST_ABS than PRE (34 ± 5 vs. 27 ± 4 min, P < 0.001), and POST_REL tended to be longer than PRE (30 ± 6 min, P = 0.053). MVC and peripheral fatigue were overall less depressed in POST_ABS than PRE at isotime. At EXH, MVC and Db_10:100 were similarly reduced in all sessions (–37 to − 42% and − 30 to − 37%, respectively). Db₁₀₀ tended to be less depressed in POST_ABS than PRE (–40 ± 9 vs. − 48 ± 16%, P = 0.050) and in POST_REL than PRE (–39 ± 9%, P = 0.071). Pt decreased similarly in POST_ABS and PRE (–52 ± 16 vs. − 54 ± 16%), but POST_REL tended to be less depressed than PRE (–48 ± 14%, P = 0.075).

Conclusions

This study confirms fatigue attenuation at isotime after training. Yet lower or similar fatigue at EXH indicates that, unlike previously suggested, fatigue tolerance may not be upregulated after 9 weeks of cycling training.

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Motivation alters implicit temporal attention through sustained and transient mechanisms: A behavioral and pupillometric study

Psychophysiology, EarlyView.


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Gestational chronodisruption leads to persistent changes in the rat fetal and adult adrenal clock and function

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Passive heat therapy protects against endothelial cell hypoxia‐reoxygenation via effects of elevations in temperature and circulating factors

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Finding the metabolic stress “sweet spot”: Implications for sprint interval training‐induced muscle remodelling

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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