TRPV4 participates in pressure-induced inhibition of renin secretion by juxtaglomerular cells

Abstract

The renin – angiotensin system is a crucial blood pressure regulation system. It consists of a hormonal cascade where the rate-limiting enzyme is renin, which is secreted in blood flow by renal juxtaglomerular (JG) cells in response to low pressure in the renal afferent arteriole. In contrast, an increase in blood pressure results in a decreased renin secretion. This is accompanied by a transitory increase in [Ca²⁺]_i of JG cells. The inverse relationship between [Ca²⁺]_i and renin secretion has been called the "calcium paradox" of renin release. How increased pressure induces a [Ca²⁺]_i transient in JG cells is however unknown. We observed that [Ca²⁺]_i transients induced by mechanical stimuli in JG As4.1 cells were completely abolished by HC067047 and RN1734, two inhibitors of TRPV4. They were also reduced by half by siRNA-mediated repression of TRPV4 but not after repression or inhibition of TRPV2 or Piezo1 ion channels. Interestingly, the stimulation of renin secretion by the adenylate cyclase activator forskolin was totally inhibited by cyclic stretching of the cells. This effect was mimicked by stimulation with GSK1016790A and 4α−PDD, two activators of TRPV4 and inhibited in the presence of HC067047. Moreover, in isolated perfused kidneys from Trpv4^−/− mice, the pressure - renin relationship was significantly altered. In vivo, Trpv4^−/− mice presented increased plasma levels of renin and aldosterone compared to wild-type mice. Altogether, our results suggest that TRPV4 is involved in the pressure-induced entry of Ca²⁺ in JG cells, which inhibits renin release and allows the negative feedback regulation on blood pressure.

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Molecular recognition at cholinergic synapses: Acetylcholine versus choline

Abstract

Acetylcholine (ACh) released at the vertebrate nerve-muscle synapse is hydrolyzed rapidly into choline (Cho), so endplate receptors (AChRs) are exposed to high concentrations of both of these structurally-related ligands. To understand how these receptors distinguish ACh and Cho, we used single-channel electrophysiology to measure resting affinities (binding free energies) of these and other agonists in adult-type mouse AChRs having a mutation(s) at the transmitter-binding sites. The aromatic rings of αY190, αW149 and αY198 each provide ∼50% less binding energy for Cho compared to ACh. At αY198 a phenylalanine substitution had no effect, but at αY190 this substitution caused a large, agonist-independent loss in binding energy that depended on the presence of αK145. The results suggest that i) αY190 is deprotonated by αK145 to strengthen the interaction between this benzene ring and the agonist's quaternary ammonium (QA) and ii) AChRs respond strongly to ACh because an H-bond positions the QA to interact optimally with the rings, and weakly to Cho because a different H-bond tethers the ligand to misalign the QA and form weaker interactions with the aromatic groups. The results suggest that the difference in ACh versus choline binding energies is determined by different ligand positions within a fixed protein structure.

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Distinct subcellular mechanisms for the enhancement of the surface membrane expression of SK2 channel by its interacting proteins, α-actinin2 and filamin A

Abstract

The normal function of ion channels depends critically on the precise subcellular localization and the number of channel proteins on the cell surface membrane. Small-conductance, Ca²⁺-activated K⁺ channels (SK, K_Ca2) are expressed in human atrial myocytes and responsible for shaping atrial action potentials. Understanding the mechanisms of SK channel trafficking may provide new insights into the regulation controlling the repolarization of atrial myocytes. We have previously demonstrated that the C and N termini of SK2 channels interact with actin-binding proteins, α-actinin2 and filamin A, respectively. However, the roles of the interacting proteins on SK2 channel trafficking remain incompletely understood. Using Total Internal Reflection Fluorescence (TIRF) microscopy, we studied the mechanisms of surface membrane localization of SK2 (K_Ca2.2) channels. When SK2 channels were co-expressed with filamin A or α-actinin2, the membrane fluorescence intensity of SK2 channels increased significantly. We next tested the effects of primaquine and dynasore on SK2 channels expression. Treatment with primaquine significantly reduced the membrane expression of SK2 channels. In contrast, treatment with dynasore failed to alter the surface membrane expression of SK2 channels. Further investigations using constitutively-active or dominant-negative forms of Rab GTPases provided additional insights into the distinct roles of the two cytoskeletal proteins on the recycling processes of SK2 channels from endosomes. α-actinin2 facilitated recycling of SK2 channels from both early and recycling endosomes while filamin A likely aids the recycling of SK2 channels from recycling endosomes.

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The effect of general anesthesia for ambulatory dental treatment on children in Chongqing, Southwest China

Summary

Background

The incidence of early childhood caries shows a significant increasing trend. Often, children younger than 6 years need additional help to finish the dental treatment. Therefore, general anesthesia (GA) could help to provide a successful environment for pediatric dental treatment.

Objectives

The aim of this study was to assess the effect of dental treatment under general anesthesia (DGA) on the patients' oral health in Chongqing, Southwest China using the P-CPQ and the FIS questionnaires.

Methods

We collected the hospital's records of the children who received DGA from 2013 to 2014 and the questionnaires answered by their parents or caregivers before and after the treatment. Then the data were integrated and analyzed to assess the effect of DGA on the children and their family, the incidence of the complications during or after DGA, and the satisfaction of their parents.

Results

We collected 659 patients' records including 55.4% boys and 44.6% girls. There were 443 children younger than 4 years, and 216 children older than 4 years. The main reason why they chose DGA was the patients' fear for the treatment (95.1%). The mean cost of DGA almost reached a half (61.5%) or a third (15.3%) of the family's monthly earning. The mean P-CPQ score and FIS score significantly decreased after DGA. The highest incidence of complications was emergence agitation, headache, and nausea/vomiting. The incidence of emergence agitation and headache was related to the operation time. The majority of families reported a high degree of satisfaction.

Conclusions

Children's oral health-related quality of life after DGA improved significantly. Meanwhile DGA showed a positive effect on the whole family and majority of families reported a high degree of satisfaction to it.

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Oral morphine dosing predictions based on single dose in healthy children undergoing surgery

Abstract

Background

Oral morphine has been proposed as an effective and safe alternative to codeine for after-discharge pain in children following surgery but there are few data guiding an optimum safe oral dose.

Aims

The aim of this study was to characterize the absorption pharmacokinetics of enteral morphine in order to simulate time–concentration profiles in children given common oral morphine dose regimens.

Methods

Children (2–6 years, n = 34) undergoing elective surgery and requiring opioid analgesia were randomized to receive preoperative oral morphine (100 mcg·kg⁻¹, 200 mcg·kg⁻¹, 300 mcg·kg⁻¹). Blood sampling for morphine assay was performed at 30, 60, 90, 120, 180, and 240 min. Morphine serum concentrations were determined by liquid chromatography–mass spectroscopy and pharmacokinetic parameters were calculated using nonlinear mixed effects models. Current data were pooled with published time–concentration profiles from children (n = 1059, age 23 weeks postmenstrual age – 3 years) administered intravenous morphine, to determine oral bioavailability (F), absorption lag time (T_LAG), and absorption half-time (T_ABS). These parameter estimates were used to predict concentrations in children given oral morphine (100, 200, 300, 400, 500 mcg·kg⁻¹) at different dosing intervals (3, 4, 5, 6, 8, 12 h).

Results

The oral morphine formulation had F 0.298 (CV 36.5%), T_LAG 0.45 (CV 63.6%) h and T_ABS 0.71 (CV 55%) h. A single-dose morphine 100 mcg·kg⁻¹ achieved a mean C_MAX 10 mcg·l⁻¹. Repeat 4-hourly dosing achieved mean steady-state concentration 13–18 mcg·l⁻¹; concentrations associated with good analgesia after intravenous administration. Serum concentration variability was large ranging from 5 to 55 mcg·l⁻¹ at steady state.

Conclusions

Oral morphine 200 mcg·kg⁻¹ then 100 mcg·kg⁻¹ 4 h or 150 mcg·kg⁻¹ 6 h achieves mean concentrations associated with analgesia. There was high serum concentration variability suggesting that respiration may be compromised in some children given these doses.

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Adrenal insufficiency in neonates after cardiac surgery with cardiopulmonary bypass

Abstract

Background

Cardiopulmonary bypass (CPB) may lead to adrenal insufficiency (AI). Emerging evidence supports association of AI with morbidity after cardiac surgery.

Aims

The aim of this study was to define AI incidence in neonates undergoing complex cardiac surgery with CPB and its association with intraoperative post-CPB outcomes.

Methods

Forty subjects enrolled in a prior randomized control trial who received preoperative methylprednisolone as part of our institutional neonatal bypass protocol were included. No intraoperative steroids were given. ACTH stimulation tests were performed: preoperatively and 1 h after separation from CPB. AI was defined as <9 μg·ml⁻¹ increase in cortisol at 30 min post cosyntropin 1 mcg. Clinical outcomes were collected up to 90 min after CPB.

Results

2/40 (5%) subjects had preoperative AI vs 13/40 (32.5%) post-CPB AI, P ≤ 0.001. No significant difference was observed in age, gestational age, weight, CPB time, circulatory arrest, or STAT category between subjects with or without post-CPB AI. ACTH decreased from preoperative values 127.3 vs 35 pcg·ml⁻¹ [median difference = 81.8, 95% CI = 22.7–127.3], while cortisol increased from 18.9 vs 75 μg·dl⁻¹ [median difference = 52.2, 95% CI = 36.3–70.9]. Post-CPB AI was associated with increased median colloid resuscitation, 275 vs 119 ml·kg⁻¹ [median difference = 97.8, 95% CI = 7.1–202.2]; higher median peak lactate, 9.4 vs 6.9 mg·dl⁻¹ [median difference = 3.2, 95% CI = 0.04–6.7]; median post-CPB lactate, 7.9 vs 4.3 mg·dl⁻¹, [median difference 3.6, 95% CI = 2.1–4.7], and median lactate on admission to CICU, 9.4 vs 6.0 mg·dl⁻¹ [median difference = 3, 95% CI = 1.1–4.9]. No difference was observed in blood pressure or vasoactive inotrope score at any time point measured in operating room (OR). Higher initial post-CPB cortisol correlated with decreased cosyntropin response.

Conclusions

Neonatal cardiac surgery with CPB and preoperative methylprednisolone leads to AI as determined by low-dose ACTH stimulation test in one-third of patients. AI is associated with increased serum lactate and colloid resuscitation in OR. Impact of preoperative methylprednisolone on results is not defined. Benefit of postoperative steroid administration in neonates with post-CPB AI warrants further investigation.

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Dexmedetomidine use in patients undergoing electrophysiological study for supraventricular tachyarrhythmias

Summary

Background

Dexmedetomidine is a selective alpha-2 adrenergic agonist with sedative, analgesic, and anxiolytic properties. Dexmedetomidine has not been approved for use in pediatrics. Dexmedetomidine has been reported to depress sinus node and atrioventricular nodal function in pediatric patients; it has been suggested that the use of dexmedetomidine may not be desirable during electrophysiological studies.

Aim

We hypothesize that the use of dexmedetomidine does not inhibit the induction of supraventricular tachyarrhythmias (SVT) during electrophysiological studies and does not inhibit the ablation of such arrhythmias.

Methods

In this retrospective, observational cohort study, we reviewed all cases presenting to the cardiac catheterization laboratory for diagnosis or treatment of SVT since 2007. All cases were performed by the same electrophysiologist. The anesthesia was provided by one of the three cardiac anesthesiologists. One cardiac anesthesiologist did not use dexmedetomidine during electrophysiological studies. A second used dexmedetomidine, but only with an infusion. The third used dexmedetomidine with a primary bolus and an infusion. Thus, the patients were stratified into three different groups: Group 1 patients did not receive any dexmedetomidine. Group 2 patients received a dexmedetomidine infusion of 0.5–1 μg·kg⁻¹·h⁻¹. Group 3 patients received a dexmedetomidine infusion of 0.5–1 μg·kg⁻¹·h⁻¹ and a dexmedetomidine bolus prior to the infusion of 0.5–1 μg·kg⁻¹. We then compared those patients for the following variables: demographic data including age, sex, height, weight; anesthetic data such as, mask vs intravenous induction, identity of induction agent, amount of sevoflurane and propofol used; amount of dexmedetomidine used; presence of congenital heart disease and other comorbidities; the need for isoproterenol and dose, the need for adenosine and dose, and the need for any other medications to affect rhythm both before and after radiofrequency ablation; the ability to induce the arrhythmia, the type of arrhythmia, the presence of Wolff–Parkinson–White syndrome, the presence of an accessory pathway, the ablation rate, and the recurrence rate.

Results

There was no difference in the anesthetic agents, except there was a lesser amount of propofol used in the dexmedetomidine groups (χ²₍₂₎ = 48.2, P < 0.001). There was no difference in the electrophysiological parameters among groups, except the Group 1 patients did require the use of isoproterenol in the preablation period less often compared to the dexmedetomidine groups (χ²₍₂₎ = 15.2, P < 0.01). However, with the greater use of isoproterenol, there was no difference in the ability to induce the arrhythmia. Moreover, the percentage of patients ablated, and the recurrence rate among groups was the same.

Conclusions

We conclude that dexmedetomidine does not interfere with the conduct of electrophysiological studies for SVT and the successful ablation of such arrhythmias. However, dexmedetomidine use did result in a greater need for isoproterenol.

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Pharmacokinetics and analgesic effectiveness of intravenous parecoxib for tonsillectomy ± adenoidectomy

Summary

Background

Few pharmacokinetic (PK) and pharmacodynamic (PD) data exist for COX-2 selective inhibitors in children. We wished to characterize the PKPD of parecoxib and its active metabolite, valdecoxib, in this population.

Methods

Children (n = 59) were randomized to parecoxib 0.25 mg·kg⁻¹, 1 mg·kg⁻¹, and 2 mg·kg⁻¹ during tonsillectomy ± adenoidectomy. Samples (4–6 per child) were obtained from indwelling cannula over 6 h. A second group of inpatient children (n = 15) given 1 mg·kg⁻¹ contributed PK data from 6 to 24 h. Pain scores and rescue medication for the first group were recorded postoperatively for up to 24 h. PK data were pooled with those (10 samples/24 h) from a published study of children (n = 38) who underwent surgery. A three-compartment parent and one-compartment metabolite model with first-order elimination was used to describe data using nonlinear mixed effects models. An E_MAX model described the relationship between dose and rescue morphine equivalents during recovery.

Results

Parecoxib PK parameter estimates were CL_PARECOXIB 19.1 L·h⁻¹·70 kg⁻¹, V1_PARECOXIB 4.2 L·70 kg⁻¹, Q2_PARECOXIB 6.29 L·h⁻¹·70 kg⁻¹, V2_PARECOXIB 130 L·70 kg⁻¹, Q3_PARECOXIB 6.02 L·h⁻¹·70 kg⁻¹, and V3_PARECOXIB 2.03 L·70 kg⁻¹. We assumed all parecoxib was metabolized to valdecoxib with CL_VALDECOXIB 9.53 L·h⁻¹·70 kg⁻¹ and V_VALDECOXIB 51 L·70 kg⁻¹. There was no maturation of clearance over the age span studied. There were no differences in pain scores between groups on waking, discharge, 12 h, or 24 h. There were no differences in analgesia consumption over 24 h between groups for tramadol, fentanyl, and morphine rescue use. Fentanyl and morphine consumption, expressed as morphine equivalents (0.13 mg·kg⁻¹) in the 0.25 mg·kg⁻¹ group, was greater than that observed in the 1 or 2 mg·kg⁻¹ groups (0.095 mg·kg⁻¹) in PACU.

Conclusions

Parecoxib 0.9 mg·kg⁻¹ in a 2-year-old, 0.75 mg·kg⁻¹ in a 7-year-old, and 0.65 mg·kg⁻¹ in a 12-year-old child achieves dose equivalence of 40 mg in a standard 70 kg person. Clearance maturation may occur in infants younger than the current cohort. Parecoxib doses above 1 mg·kg⁻¹ add no additional analgesia.

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Mortality following congenital diaphragmatic hernia repair: the role of anesthesia

Abstract

Background

Mortality following surgical repair of congenital diaphragmatic hernia (CDH) remains high. The volume and type of perioperative intravenous fluid administered, baro-trauma, oxygen toxicity, and the duration of anesthesia are thought to affect outcome in surgical populations.

Aims

The aim of this retrospective observational study was to determine whether the perioperative volume or type of fluids and/or the duration of anesthesia were associated with postoperative mortality and if mortality was predicted by the oxygenation index (OI) prior to or following CDH surgical repair.

Methods

The records of infants with a left-sided CDH and without other congenital anomalies, who underwent surgical repair between April 2009 and March 2015, were examined. The oxygenation index was used to "quantify" the severity of lung function abnormality and reported as the best OI on day 1 after birth (OI_BEST), the OI immediately prior to surgery (OI_PRE) and at 1, 6, 12, and 24 h postsurgery (OI_1h, OI_6h, OI_12h, OI_24h), respectively. The change in the OI index (delta OI) was calculated by subtracting OI_PRE from postoperative OIs.

Results

The records of 37 CDH infants (median gestational age 35.8, range 31.5–41.4 weeks) were assessed; six died postoperatively. Neither the duration of anesthesia, the volume of crystalloids or colloids administered, nor the peak inflation pressures used during surgical repair were significantly correlated with postoperative mortality. Neither fetal tracheal occlusion nor use of a parietal patch significantly influenced mortality. The postoperative OI_1h, OI_6h, OI_12h showed weak evidence for a difference between survivors and nonsurvivors. An OI_24h of ≥5.5 predicted mortality with 100% sensitivity (95% CI, confidence intervals (CI) 40–100) and 93.1% specificity (95% CI, 77–99).

Conclusion

Neither the volume of intraoperative fluids administered nor the duration of anesthesia was associated with postoperative death. The OI 24 h postsurgery was the best predictor of an increased risk of mortality.

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Codeine use among children in the United States: a nationally representative study from 1996 to 2013

Summary

Background

Concerns regarding the safety of codeine have been raised. Cases of life-threatening respiratory depression and death in children have been attributed to codeine's polymorphic metabolic pathway. International health agencies recommend restricted use of codeine in children. Despite these recommendations, the epidemiology of codeine use among children remains unknown.

Aims

Our objective was to examine patterns of codeine use in the US among children.

Methods

A cross-sectional analysis of children of age 0–17 years from 1996 to 2013 in the US was performed. Data were extracted from MEPS, a nationally representative set of health care surveys. Prevalence rates of codeine use between 1996 and 2013 were examined. Multivariable logistic regression examined relationships between codeine use and patient demographics.

Results

Codeine use remained largely unchanged from 1996 to 2013 (1.08 vs 1.03 million children, respectively). Odds of codeine use was higher in ages 12–17 (OR, 1.40; [1.21–1.61]), outside of the Northeastern US, and among those with poor physical health status (OR, 3.29 [1.79–6.03]). Codeine use was lower in children whose ethnicity was not white and those uninsured (OR, 0.47 [0.34–0.63]). Codeine was most frequently prescribed by emergency physicians (18%) and dentists (14%). The most common condition associated with codeine use was trauma-related pain.

Conclusions

Pediatric codeine use has declined since 1996; however, more than 1 million children still used codeine in 2013. Health care providers must be made aware of guidelines advising against the use of codeine in children. Codeine is potentially hazardous and safer alternatives to treat children's pain are available.

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Evaluation of I-Gel™ size 2 airway in different degrees of neck flexion in anesthetized children – a prospective, self-controlled trial

Summary

Background

A previous study by our group demonstrated an increase in oropharyngeal leak pressures and a deterioration of ventilation in maximum neck flexion with the I-Gel^™. To ascertain the optimal degree of neck flexion which increases OPLP without compromising ventilation we conducted a prospective self-controlled trial with the I-Gel^™ in different degrees of neck flexion in anesthetized paralyzed children.

Methodology

The I-gel^™ was inserted in 60 children undergoing inhalation induction with muscle paralysis for routine general anesthesia. Recordings of peak inspiratory pressures (PIP) at flexion of 15°, 30°, and 45° were taken as the primary outcome. Expired tidal volume, ventilation scoring, fiberoptic gradings, and OPLP in different degrees of flexion were recorded as secondary outcomes.

Results

There was a significant increase in mean PIP in cm H₂O at flexion 30° [13.3 (95% CI 12.8–13.8) cm H₂O, P < 0.001] and 45° flexion (16.5 [15.9–17.1] cm H₂O, P < 0.001) compared to neutral. A decrease in the expired tidal volume was seen at flexion of 30° (7.6 [7.3–7.8] cm H₂O, P = 0.00) and 45° (7.6 [7.3–7.8] cm H₂O, P = 0.00). There was deterioration of ventilation score, mean [range] at 30° flexion 2[0–3], and 45° flexion 1[0–3] compared to the neutral 3[2–3]. There was a significant increase in OPLP with an increase in degree of flexion.

Conclusion

We conclude that 15° neck flexion can safely be applied without compromising ventilation with the I-Gel^™ in anesthetized paralyzed children. However, Flexion of 30° or more warrants caution or the use of alternative devices like an endotracheal tube due to increase in PIP and worsening of ventilation score.

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A retrospective comparison of propofol alone to propofol in combination with dexmedetomidine for pediatric 3T MRI sedation

Abstract

Background and aim

Both propofol and dexmedetomidine have been found to be safe and effective sedation for magnetic resonance imaging (MRI). Our program experienced an increase in patients arousing and experiencing an adverse airway event during propofol sedation for MRI in the first months of using a new 3T (Tesla) MRI scanner that was found to have a longer reverberation time compared to the previous 1.5 T MRI. In an effort to decrease patient arousal and adverse airway events during MRI, we administered a dexmedetomidine load prior to our standard propofol protocol. The objective was to compare adverse events and other outcome measures of patients sedated with propofol alone (Pro) and propofol preceded by a dexmedetomidine load (D+P).

Methods

We reviewed a sedation database and medical records for all children undergoing 3T MRI studies while sedated with propofol alone or propofol preceded by a dexmedetomidine load in 2014.

Results

Two hundred and fifty-six sedations were performed for MRI (87 Pro and 169 D+P). The two groups were comparable with regard to age, weight, gender, and American Society of Anesthesiologists status. Subjects in the D+P cohort had significantly fewer adverse events (10/169 patients (5.9%) vs 23/87 patients (26.4%) [OR 0.18, 95% CI: 0.08–0.39, P < 0.001]), particularly upper airway obstruction. Mean discharge time was longer in the D+P cohort compared to the Pro cohort (87.1, SD 26.3 min vs 69.7, SD 23.6; [mean difference 17.7 min, 95% CI: 10.6–24.8, P < 0.001]).

Conclusions

The addition of a dexmedetomidine infusion prior to our propofol MRI sedation protocol resulted in fewer sedation-related adverse events, particularly upper airway obstruction. Further studies are needed to evaluate the potential for a reduction on adverse events with this drug combination.

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Clinical profile and prognosis of patients with posterior circulation stroke

2016-10-25T04-38-40Z
Source: International Journal of Research in Medical Sciences
Kavita J. Rawat, Bhaskar S. Korde, Kavita S. Joshi.
Background: Posterior circulation stroke is less common than stroke involving the anterior circulation. An understanding of the Posterior circulation stroke phenomenology and mechanisms requires knowledge of neurovascular anatomy and of the structure-function relationships of this region of the brain. Identifying mechanisms of stroke is essential so that appropriate preventive therapies may be instituted. Methods: A prospective study was conducted over a period of 1 year after obtaining permission from institutional ethics committee. Recently diagnosed cases of posterior circulation stroke from medicine and neurology wards were enrolled, who fulfilled inclusion criteria. Results: Most common age for posterior circulation stroke in this study was 41-70 years of age with median age of 56.5 years. It is more common in males (55%) than females (45%). Ischemic posterior circulation stroke is more common (63.15%) than haemorrhagic posterior circulation stroke (36.85%). Most common presenting feature of posterior circulation was ataxia (77.3%). Most common risk factor for posterior circulation stroke was hypertension (60.5%) followed by dyslipidemia (55.26%). Most common site of involvement in ischemic posterior circulation stroke was cerebellum (37.5%) followed by occipital lobe (24%). Commonest site of bleed found was cerebellum (64.4%) followed by pons (35.6%). Mortality in posterior circulation stroke in present study was 15.78%. Conclusions: Posterior circulation stroke present with a wide variety of symptoms. Episodes are often staggering and more protracted than those of anterior circulation stroke. Further studies are needed to determine the safest and most effective treatment modalities for the various types of posterior circulation stroke.


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A clinical study of deviated nasal septum with special reference to conventional and endoscopic septoplasty

2016-10-25T04-38-40Z
Source: International Journal of Research in Medical Sciences
Mohammad Nizamuddin Khan, Kripamoy Nath, Shams Uddin.
Background: Deviated nasal septum is a very common condition. It causes nasal obstruction, epistaxis, sinusitis, headache and obstructive sleep apnea. Septoplasty is one of the most common procedures performed for correction of deviated nasal septum. The aim of our study was to determine the incidence of DNS with respect to age, sex, type of septal deviation and presenting complaints and compare if endoscopic septoplasty is better than conventional septoplasty. Methods: The present study was conducted among 115 cases of DNS for a period of one year. While detailed clinical study was done in 115 cases, surgery was performed in 60 cases. They were divided into group A and group B with 30 cases in each group. Conventional septoplasty was performed in group A while endoscopic septoplasty in group B. Results: The male to female ratio was found to be 2.19:1. Majority (37.18%) patients were of age group 11-20 years with deviation to the left (54.78%). Nasal obstruction (58.26%) was the commonest presenting complaint. Postoperatively, a significant relief of symptoms were observed in endoscopic septoplasty in terms of nasal obstruction (93.33%) and hyposmia (87.5%). Post-operative complications were higher in conventional septoplasty with significant rate of residual deviation. Conclusions: Our study showed that functional outcome was better and post-operative complications were less in endoscopic septoplasty. Endoscopic septoplasty provides better illumination which helps to identify septal deviation accurately while reducing the postoperative complications due to limited dissection and lesser trauma to septal cartilage.


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Single umbilical artery with antenatally diagnosed umbilical artery aneurysm in a newborn: a rare case report

2016-10-25T04-20-12Z
Source: International Journal of Contemporary Pediatrics
Ankur Gupta, Dhrithiman Shetty, Prijo Philip.
Single umbilical artery (SUA) is a situation when the umbilical cord contains only one umbilical artery rather than normally occurring two umbilical arteries. Presence of a SUA is associated with an increased risk of perinatal morbidity and mortality. This article reports a case of SUA with antenatally diagnosed umbilical artery aneurysm and its significance in a newborn. Histopathology report from site of insertion of umbilical cord to placenta had shown single umbilical artery aneurysm and persistent vitilo intestinal duct, dilated umbilical artery at insertion of the cord at placenta. ECHO report suggested 7 mm ostium secondum atrial septal defect, 3-4 mm patent ductus arteriosus, dilated right atria and ventricle, severe tricuspid regurgitation, severe pulmonary artery hypertension. Karyotyping was reported to be normal. Child had received treatment for congestive cardiac failure and intravenous antibiotics for Klebsiella sepsis. SUA with antenatally diagnosed umbilical artery aneurysm is a rare entity and has to be thoroughly investigated and treated.


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Integrating Self-Determination and Job Demands–Resources Theory in Predicting Mental Health Provider Burnout

Abstract

Limited progress has been made in reducing burnout in mental health professionals. Accordingly, we identified factors that might protect against burnout and could be productive focal areas for future interventions. Guided by self-determination theory, we examined whether supervisor autonomy support, self-efficacy, and staff cohesion predict provider burnout. 358 staff from 13 agencies completed surveys. Higher levels of supervisor autonomy support, self-efficacy, and staff cohesion were predictive of lower burnout, even after accounting for job demands. Although administrators may be limited in their ability to reduce job demands, our findings suggest that increasing core job resources may be a viable alternative.

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Prevalence and predictors of obesity-related counseling provided by outpatient psychiatrists in the United States

Psychiatric Services

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Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): Results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial

The Lancet Oncology

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New research verifies TASINs as viable target for colon cancer therapies

UT Southwestern Medical Center

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Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication

Journal of Hepatology

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Impact of BMI on ability to successfully create an IPAA

Diseases of the Colon and Rectum

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The impact of proton pump inhibitor therapy on patients with liver disease

Alimentary Pharmacology and Therapeutics

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High-flow haemangiomas versus hypervascular hepatocellular carcinoma showing pseudo-washout on gadoxetic acid-enhanced hepatic MRI: Value of diffusion-weighted imaging in the differential diagnosis of small lesions

Clinical Radiology

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Metformin confers risk reduction for developing hepatocellular carcinoma recurrence after liver resection

Liver International

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Differential changes in gut microbiota after gastric bypass and sleeve gastrectomy bariatric surgery vary according to diabetes remission

Obesity Surgery

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Third-line chemotherapy with irinotecan plus 5-fluorouracil in Caucasian metastatic gastric cancer patients

Oncology

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Febrile neutropenia with thrombocytopenia after infliximab induction in a patient with ulcerative colitis

Case Reports in Gastroenterology

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Usefulness of combination therapy with Daclatasvir plus Asunaprevir in chronic hepatitis C patients with chronic kidney disease

Clinical and Experimental Nephrology

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Patients perceive clinical benefit with the specific carbohydrate diet for inflammatory bowel disease

Digestive Diseases and Sciences

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Hepatic vein arrival time for diagnosis of liver cirrhosis: A 10-year single-center experience with contrast-enhanced sonography

Journal of Ultrasound in Medicine

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Risk-adjusted treatment selection and outcome of patients with acute cholecystitis

Langenbeck's Archives of Surgery

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Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia

Neurogastroenterology & Motility

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Radiofrequency ablation and transarterial chemoembolisation as first-line treatment for recurrent hepatocellular carcinoma or isolated intrahepatic recurrent hepatocellular carcinoma in transplanted livers

Clinical Radiology

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Fast track for open hepatectomy: A systemic review and meta-analysis

International Journal of Surgery

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Prediction model for hemorrhagic complications after laparoscopic sleeve gastrectomy: Development of sleeve bleed calculator

Obesity Surgery

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Use of direct-acting agents for HCV-positive kidney-transplant candidates and kidney-transplant recipients

Transplant International

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Issue Information - Editorial Board

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Influence of Medical Insurance Under the Affordable Care Act on Access to Pain Management of the Trauma Patient.

Background and Objectives: The Affordable Care Act intended to "extend affordable coverage" and "ensure access" for vulnerable patient populations. This investigation examined whether the type of insurance (Medicaid, Medicare, Blue Cross, cash pay) carried by trauma patients influences access to pain management specialty care. Methods: Investigators phoned 443 board-certified pain specialists, securing office visits with 235 pain physicians from 8 different states. Appointments for pain management were for a patient who sustained an ankle fracture requiring surgery and experiencing difficulty weaning off opioids. Offices were phoned 4 times assessing responses to the 4 different payment methodologies. Results: Fifty-three percent of pain specialists contacted (235 of 443) were willing to see new patients to manage pain medication. Within the 53% of positive responses, 7.2% of physicians scheduled appointments for Medicaid patients, compared with 26.8% for cash-paying patients, 39.6% for those with Medicare, and 41.3% with Blue Cross (P

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Ultrasound-Guided Cervical Medial Branch Radiofrequency Neurotomy: Can Multitined Deployment Cannulae Be the Solution?.

Background and Objectives: Novel multitined cannulae constitute an attractive option for ultrasound-guided radiofrequency neurotomy of cervical medial branches. The deployment tines increase the cannula's active area, thus altering its lesion size. Despite their theoretical benefits, multitined cannulae have not been assessed. In this bench study, we sought to investigate the lesions produced by a standard 18-gauge and 2 commercially available multitined deployment cannulae. We created ex vivo models to evaluate lesion morphology at a periosteal interface using approach angles likely to be encountered during an ultrasound-guided technique. Methods: Two ex vivo models were assembled using chicken breast tissue and bovine tibia. Monopolar lesions were carried out with 3 commercially available cannulae (18-gauge curved [S], 17-gauge with laterally deploying tines [N], and 18-gauge with distally deploying tines [T]). All cannulae were positioned at 0, 25, 45, and 90 degrees to the periosteal plane. For each angulation and cannula, 2 series of measurements were recorded to document lesion morphology in the axial and sagittal planes. Data collected included the lesion's surface area, shape, and dimensions relative to the needle tip. Results: A total of 240 lesions were analyzed. The performances of S and N cannulae were significantly affected by approach angle, with lesion size decreasing as the angle increased. In contrast, T cannulae displayed similar lesion surface areas at 0 and 90 degrees. The multitined N and T cannulae produced the largest lesions at 0/25 and 90 degrees, respectively. Lesion height varied inversely according to approach angle for S and N cannulae, whereas T cannulae displayed stable characteristics. Conclusions: Unlike their S and N counterparts, T cannulae demonstrated stable lesion characteristics at varying approach angles. Copyright (C) 2016 by American Society of Regional Anesthesia and Pain Medicine.

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Fluorescent incisionless cholangiography as a teaching tool for identification of Calot’s triangle

Abstract

Background

Intraoperative incisionless fluorescent cholangiogram (IOIFC) has been demonstrated to be a useful tool to increase the visualization of Calot's triangle. This study evaluates the identification of extrahepatic biliary structures with IOIFC by medical students and surgery residents.

Methods

Two pictures were taken, one with xenon light and one with near-infrared (NIR) light, at the same stage during dissection of Calot's triangle in ten different cases of laparoscopic cholecystectomy (LC). All twenty pictures were organized in a random fashion to remove any imagery bias. Twenty students and twenty residents were asked to identify the biliary anatomy.

Results

Medical students were able to accurately identify the cystic duct on an average 33.8 % under the xenon light versus 86 % under NIR light (p = 0.0001), the common hepatic duct (CHD) on an average 19 % under the xenon light versus 88.5 % under NIR light (p = 0.0001), and the junction on an average 24 % under xenon light versus 80.5 % under NIR light (p = 0.0001). Surgery residents were able to accurately identify the cystic duct on an average 40 % under the xenon light versus 99 % under NIR light (p = 0.0001), the CHD on an average 35 % under the xenon light versus 96 % under NIR light (p = 0.0001), and the junction on an average 24 % under the xenon light versus 95.5 % under NIR light (p = 0.0001).

Conclusions

IOIFC increases the visualization of Calot's triangle structures when compared to xenon light. IOIFC may be a useful teaching tool in residency programs to teach LC.

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Visceral to subcutaneous fat ratio predicts acuity of diverticulitis

Abstract

Introduction

There is an association between obesity and more complicated diverticular disease. We hypothesize that this link may be due to an increased level of visceral fat rather than an elevated body mass index alone. Adipose tissue secretes inflammatory cytokines, and chronic inflammation may account for the link between obesity and a more severe presentation of diverticular disease. We have applied a quantitative measure of visceral fat content in a series of patients admitted with diverticulitis, comparing those who required emergent versus elective surgical procedures for diverticulitis.

Methods

We performed a retrospective review of all adult patients who underwent emergent or elective surgery at our institution for diverticulitis from 2010 to 2014. Data were collected on demographics, comorbidities, operative findings, complications, and length of stay. Radiologic measurements of adiposity were obtained from preoperative CT scans. Visceral fat areas and subcutaneous fat areas were measured, and the V/S ratio was calculated.

Results

Thirty-four patients underwent emergent and 32 patients underwent elective surgery. The mean age was 66.3 years for the emergent and 57.11 for the elective group (p = 0.04178). The perinephric, visceral, subcutaneous fat, and V/S ratio for the emergent group were 1.71, 185.22, 338.22, and 0.56 and were 1.11, 127.18, 295.28, and 0.46 for the elective group. The difference between the V/S ratio for each group was significant (p = 0.0238). The emergent group had an average LOS of 16.11 days compared to 5.15 for the elective group (p = <0.00001). The complication rate was significantly higher (p = 0.024) in the emergent group (n = 12, 35.2 %) compared to the elective group (n = 4, 12.5 %).

Conclusion

Our study demonstrates a clinically significant link between visceral fat and severity of presentation of diverticulitis. Patients with higher V/S fat ratios were more likely to require emergency surgery and have more complications and a longer LOS.

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Multi-port versus single-port cholecystectomy: results of a multi-centre, randomised controlled trial (MUSIC trial)

Abstract

Background

Single-port laparoscopic surgery as an alternative to conventional laparoscopic cholecystectomy for benign disease has not yet been accepted as a standard procedure. The aim of the multi-port versus single-port cholecystectomy trial was to compare morbidity rates after single-access (SPC) and standard laparoscopy (MPC).

Methods

This non-inferiority phase 3 trial was conducted at 20 hospital surgical departments in six countries. At each centre, patients were randomly assigned to undergo either SPC or MPC. The primary outcome was overall morbidity within 60 days after surgery. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov (NCT01104727).

Results

The study was conducted between April 2011 and May 2015. A total of 600 patients were randomly assigned to receive either SPC (n = 297) or MPC (n = 303) and were eligible for data analysis. Postsurgical complications within 60 days were recorded in 13 patients (4.7 %) in the SPC group and in 16 (6.1 %) in the MPC group (P = 0.468); however, single-access procedures took longer [70 min (range 25–265) vs. 55 min (range 22–185); P < 0.001]. There were no significant differences in hospital length of stay or pain VAS scores between the two groups. An incisional hernia developed within 1 year in six patients in the SPC group and in three in the MPC group (P = 0.331). Patients were more satisfied with aesthetic results after SPC, whereas surgeons rated the aesthetic results higher after MPC. No difference in quality of life scores, as measured by the gastrointestinal quality of life index at 60 days after surgery, was observed between the two groups.

Conclusions

In selected patients undergoing cholecystectomy for benign gallbladder disease, SPC is non-inferior to MPC in terms of safety but it entails a longer operative time. Possible concerns about a higher risk of incisional hernia following SPC do not appear to be justified. Patient satisfaction with aesthetic results was greater after SPC than after MPC.

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Laparoscopic colorectal cancer resections in the obese: a systematic review

Abstract

Background

Laparoscopic colorectal cancer operations in obese patients pose technical challenges that may negatively impact oncologic adequacy. A meta-analysis was performed to assess the oncologic outcomes of laparoscopic colorectal cancer resections in obese compared to non-obese patients. Short- and long-term outcomes were assessed secondarily.

Methods

A systematic literature search was conducted from inception until October 01, 2014. Studies that compared outcomes of laparoscopic colorectal malignant neoplasms in obese and non-obese patients were selected for meta-analysis. Studies that defined obesity as body mass index (BMI) ≥ 30 kg/m² were included. Oncologic, operative, and postoperative outcomes were evaluated. Pooled odds ratios (OR) and weighted mean differences (WMD) with 95 % confidence intervals (CI) were calculated using fixed-effects models. For oncologic and survival outcomes, a subgroup analysis was conducted for rectal cancer and a secondary analysis was conducted for Asian studies that used a BMI cutoff of 25 kg/m².

Results

Thirteen observational studies with a total of 4550 patients were included in the meta-analysis. Lymph node retrieval, distal, and circumferential margins, and 5-year disease-free and overall survival were similar in the obese and non-obese groups. Conversion rate (OR 2.11, 95 % CI 1.58–2.81), postoperative morbidity (OR 1.54, 95 % CI 1.21–1.97), wound infection (OR 2.43, 95 % CI 1.46–4.03), and anastomotic leak (OR 1.65, 95 % CI 1.01–2.71) were all significantly increased in the obese group.

Conclusions

Laparoscopic colorectal cancer operations in obese patients pose an increased technical challenge as demonstrated by higher conversion rates and higher risk of postoperative complications compared to non-obese patients. Despite these challenges, oncologic adequacy of laparoscopic colorectal cancer resections is comparable in both groups.

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Central Factors Contribute to Knee Extensor Strength Loss after 2000-m Rowing in Elite Male and Female Rowers.

Purpose: Despite growing interest in task-dependent alterations of central and peripheral fatigue following endurance exercise, little is known about the impact of rowing on quadriceps muscle fatigue. This study aimed to investigate central and peripheral mechanisms of fatigue following a 2000-m rowing time-trial. Methods: Eight competitive rowers (4 males, 4 females, 20 +/- 4 years) performed a 2000-m time-trial on an indoor rower and a control condition (sitting). Neuromuscular function of the knee extensors was analyzed prior to and 3 min after each experimental condition. Maximal voluntary torque, voluntary activation and normalized root mean square of the EMG signal were measured during isometric and concentric contractions. Furthermore, knee extensor twitch torque and maximal M-wave amplitudes in response to electrical nerve stimulation were assessed. Results: After 2000-m rowing, there were significant reductions in isometric and concentric maximal voluntary torque of the knee extensors (-20 +/- 9%; -18 +/- 7%; P

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Muscular and Aerobic Fitness, Working Memory, and Academic Achievement in Children.

PURPOSE: This study investigated the relationship between aerobic and muscular fitness with working memory and academic achievement in preadolescent children. METHODS: Seventy-nine 9-11 year old children completed an aerobic fitness assessment using a graded exercise test; a muscular fitness assessment consisting of upper body, lower body, and core exercises; a serial n-back task to assess working memory; and an academic achievement test of mathematics and reading. RESULTS: Hierarchical regression analyses indicated that after controlling for demographic variables (age, sex, grade, IQ, SES), aerobic fitness was associated with greater response accuracy and d' in the 2-back condition and increased mathematic performance in algebraic functions. Muscular fitness was associated with increased response accuracy and d', and longer RT in the 2-back condition. Further, the associations of muscular fitness with response accuracy and d' in the 2-back condition were independent of aerobic fitness. CONCLUSION: The current findings suggest the differential relationships between aerobic and muscular aspects of physical fitness with working memory and academic achievement. With the majority of research focusing on childhood health benefits of aerobic fitness, this study suggests the importance of muscular fitness to cognitive health during preadolescence. (C) 2016 American College of Sports Medicine

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Aerobic Exercise Training Modalities and Prediabetes Risk Reduction.

PURPOSE: Prediabetes is linked to several modifiable risk factors, in particular, physical activity participation. The optimal prescription for physical activity remains uncertain. This pilot study aimed to investigate the effectiveness of continuous moderate intensity (CON) versus high intensity interval (HIIT) aerobic training in persons with prediabetes. Outcome measures included hemoglobin A1c (A1C), body composition, musculoskeletal and aerobic fitness. METHODS: Participants (n= 35) were recruited and screened using a questionnaire plus capillary blood point-of-care A1C analysis. After baseline screening/exclusions, 21 participants were randomly assigned to either HIIT or CON training 3X per week for twelve weeks. All participants also undertook resistance training 2X per week. A1C, an oral glucose tolerance test, select measures of physical and physiological fitness were assessed at baseline and follow-up. RESULTS: There were no significant differences in improvements in select metabolic indicators to training between CON and HIT groups. Pooled participant data showed a mean reduction in A1C of 0.5% (95%CI 0.3-0.7%), while [beta]-cell function (%[beta]) improved by 28.9% (95%CI 16.5-39.2%) and insulin sensitivity (%S) decreased by 34.8 (95%CI 57.8-11.8), as assessed by HOMA. Significant reductions in waist circumference of 4.5cm (p

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THE EFFECT OF SHOULDER PAD DESIGN ON HEAD IMPACT SEVERITY DURING CHECKING.

Introduction: Shoulder-to-head contact is the most common cause of concussions in ice hockey, accounting for 42% of cases in the National Hockey League (NHL). The goal of this project was to determine how shoulder pad stiffness, modified by adding foam padding over the shoulder cap of existing shoulder pads, affected head impact severity when participants delivered checks to an instrumented dummy. Methods: Fifteen participants administered "the hardest shoulder checks they were comfortable delivering" to the head of a dummy equipped with tri-axial accelerometers and gyros mounted in its helmet. Trials were conducted with participants wearing two common types of shoulder pads, with and without a 2 cm thick layer of polyurethane foam over the shoulder pad cap. Results: When participants delivered checks with foam-modified pads versus unmodified pads, there was a decrease of 25.0% in the average peak linear head acceleration (28.73 versus 38.31 g; mean difference = 9.58 g, 95% CI: 6.35 - 12.81; p

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Construct Validity of the Neighborhood Environment Walkability Scale for Africa.

Purpose: Development of valid measures of built environments relevant for physical activity is an important step toward controlling the global epidemic of physical inactivity-related non-communicable diseases and deaths. This study assessed the construct validity of a self-report neighborhood environment walkability scale adapted for Africa (NEWS-Africa), by examining relationships with self-reported walking for transportation and recreation using pooled data from six sub-Saharan African countries. Methods: NEWS was systematically adapted to assess urban, peri-urban and rural environments in sub-Saharan Africa. Adults (n=469, 18-85 years, 49.7% women) from Cameroon, Ghana, Mozambique, Nigeria, South Africa and Uganda were purposively recruited from neighborhoods varying in walkability and socioeconomic status, with some from villages. Participants completed the 76-item (13 subscales) NEWS-Africa by structured interview and reported weekly minutes of walking for transport and recreation using items from the International Physical Activity Questionnaire. Results: The overall 'walkability' index had a positive relationship with both walking for transportation (eta2=0.020, p=0.005) and recreation (eta2=0.013, p=0.028) in the pooled analyses. The mixed-use access and stranger-danger scales were positively related with transport walking (eta2=0.020, p=0.006 and eta2=0.021, p=0.040, respectively). Proximity of recreational facilities (eta2=0.016, p=0.015), road/path connectivity (eta2=0.025, p=0.002), path infrastructure (eta2=0.021, p=0.005), and overall places for walking and cycling (eta2=0.012, p=0.029) scales were positively related to recreational walking. Country-specific results were mostly non-significant except for South Africa and Uganda. Conclusions: Seven of 14 NEWS-Africa scales were significantly related to walking behavior in pooled analyses, providing partial support for the construct validity of NEWS-Africa. However, effect sizes appeared to be lower than those from other continents. Further study with larger and more diverse samples is needed to determine whether the instrument performs well in each country. (C) 2016 American College of Sports Medicine

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Relative efficacy of nicotinamide treatment of a mouse model of infantile Niemann-Pick C1 disease

Abstract

Nicotinamide delivered in drinking water at about 2 g/kg/day significantly prolonged survival and showed a suggestive improvement on memory in the Npc1 ^nih/ Npc1 ^nih mouse model of infantile NPC1 disease. It is likely that this role is due to its function as a histone deacetylase (HDAC) inhibitor although another HDAC inhibitor, valproic acid, was without effect. Nicotinamide could also work by preventing/reversing oxidative stress.

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Negativity bias for sad faces in depression: An event-related potential study

Publication date: Available online 24 October 2016
Source:Clinical Neurophysiology
Author(s): Qin Dai, Juanjuan Wei, Xiaorui Shu, Zhengzhi Feng
ObjectiveNegativity bias in depression has been previously confirmed. However, mainly during a valence category task, it remains unclear how happy or unhappy individuals perceive emotional materials. Moreover, cerebral alteration measurements during a valence judgment task were lacking. The present study aimed to explore a valence judgment of a valence rating task, combined with event-related potential (ERP) recording.MethodsHealthy controls, individuals with sub-clinical depression, and patients diagnosed with major depressive disorder (MDD) were recruited. Twenty-four subjects in each group completed a valence rating task, during which the ERP amplitudes were recorded.ResultsThe MDD group had lower valence scores, faster responses, and greater N1 amplitudes for sad faces, whereas individuals with sub-clinical depression had faster responses and greater P1 amplitudes for all faces but lower valence scores and greater P2 amplitudes for happy faces.ConclusionsThe findings suggest the tendency toward a negativity bias in valence ratings in patients with depression supported by behavioral and cerebral evidence which is a latent trait of depression, possibly associated with the vulnerability of depression.SignificanceThe current study offers the first experimental evidence of cognitive and cerebral biomarkers of negativity bias in valence ratings in depression, which confirms Beck's cognitive theory and gives important direction for clinical therapy.



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