Effect of intradialytic oral nutritional supplementation on nutritional markers in malnourished chronic hemodialysis patients: prospective randomized trial.

BACKGROUND AND OBJECTIVES: Malnutrition is prevalent in chronic hemodialysis (HD) patients. It increases mortality and negatively affects quality of life. This study aimed to assess the effect of intradialytic oral nutritional supplement (ONS) on nutritional markers in chronic HD patients with protein energy wasting (PEW). METHODS: This 3-month prospective, open-label, randomized controlled trial included 60 chronic HD patients with PEW. The intervention group (30 patients) received intradialytic ONS and dietary counseling, whereas the control group (30 patients) received only dietary counseling. Nutritional markers were measured at the beginning and end of the study. RESULTS: The mean age of the patients was 54 ± 12.7 years, and that of the HD vintage was 64 ± 49.3 months. Compared to the control group, the intervention group showed a significant increase in serum albumin (p < 0.001), prealbumin (p < 0.001), cholesterol (p = 0.016), body mass index (BMI) (p = 0.019), serum creatinine/body surface area (BSA) (p = 0.016), and composite French PEW score (p = 0.002), as well as a significant decrease in high-sensitivity C-reactive protein (hs-CRP) (p = 0.001). The total iron binding capacity, normalized protein nitrogen appearance, and hemoglobin levels increased significantly in both groups. CONCLUSION: Intradialytic ONS and dietary counseling for three months were more effective than dietary counseling alone in terms of improving nutritional status and inflammation in chronic HD patients, as evidenced by increases in serum albumin, prealbumin, BMI, serum creatinine/BSA, composite French PEW score, and a decrease in hs-CRP.

ACR Appropriateness Criteria® Staging and Follow-up of Primary Vaginal Cancer.

Primary vaginal cancer is rare, comprising 1% to 2% of gynecologic malignancies and 20% of all malignancies involving the vagina. More frequently, the vagina is involved secondarily by direct invasion from malignancies originating in adjacent organs or by metastases from other pelvic or extrapelvic primary malignancies. Data on the use of imaging in vaginal cancer are sparse. Insights are derived from the study of imaging in cervical cancer and have reasonable generalizability to vaginal cancer due to similar tumor biology. Given the trend toward definitive chemoradiation for both cancers in all but early stage lesions, principles of postchemoradiation tumor response evaluation are largely analogous. Accordingly, many of the recommendations outlined here are informed by principles translated from the literature on cervical cancer. For pretreatment assessment of local tumor burden and in the case of recurrent vaginal cancer, MRI is the preferred imaging modality. PET/CT has demonstrated utility for the detection of nodal metastatic and unexpected distant metastatic disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Comparison of Heat Shock Protein 70 Expression in Response to Different Non-Ablative Lasers: An In Vitro Study.

Objective: The objective of our in vitro study was to compare the extent and timing of heat shock protein 70 (HSP70) expression following non-ablative fractional laser (NAFL) Er:Glass as well as Nd:YAG and alexandrite laser systems. Background: The role of HSP70 has been established in wound healing. Reports indicate that HSP70 expression increases after skin laser interventions. Methods: Human skin ex vivo explants were subjected to different fluences and pulse durations by using the three laser systems. Assessments were conducted on days 0, 1, 3, and 5 post-laser intervention. HSP70 expression was assessed by immunohistochemistry using anti-HSP70. Results: Er:Glass interventions caused the most significant increase in HSP70 expression whereas alexandrite interventions resulted in the least HSP70 expression, although significant compared with controls. HSP70 expression rose rapidly and dissipated quickly after Er:Glass and Nd:YAG interventions. Epidermal damage was most noted after Er:Glass interventions followed by the Nd:YAG and alexandrite systems. Conclusions: Non-ablative laser systems induce the expression of HSP70. Therefore, laser treatment may be considered 1-3 days before anticipated skin trauma to minimize scar formation provided the future validation of our data in an in vivo setting. The NAFL Er:Glass has the most potential for HSP70, yet it has also the most potential for complications.

Treating Field Cancerization by Ablative Fractional Laser and Indoor Daylight: Assessment of Efficacy and Tolerability.

Objective: To assess if ablative fractional laser combined with indoor daylight photodynamic therapy are effective and safe for the treatment of skin field cancerization associated with actinic keratosis (AK). Methods: A total of 46 patients with field cancerized skin and AK were treated by a single session of laser assisted drug delivery (LAAD) and indoor daylight photodynamic therapy (IDL-PDT). LAAD was applied using a CO2 ablative fractional laser (AFXL) and aminolevulonic acid. Thereafter, IDL-PDT was administered using a novel device that mimics the sun radiation with a total dose of 48 J/cm². Results: All patients showed remission following subsequent to the study protocol (complete: 71.7%, partial: 28.3%). Pain scores using a visual analog scare immediately following treatments were 9.0 ± 2.0. Conclusions: AFXL-LAAD combined with IDL-PDT is extremely effective for the treatment of skin field cancerization associated with AK. Nevertheless, the high pain scores associated with this combined approach may prove to be a limiting factor. Thus, further protocol modifications in larger scale studies are still warranted. J Drugs Dermatol. 2020;19(3):425-427. doi:10.36849/JDD.2020.4589.

Stimulation of collagen and elastin production in-vivo using 1,540 nm Er:Glass laser: assessment of safety and efficacy.

Introduction: Induction of collagen and elastin remodeling in the human skin can be achieved by non-ablative fractional laser (NAFXL) and ablative fractional laser (AFXL). Our objective was to compare the safety, efficacy, tolerability, and ability to induce collagen and elastin remodeling of NAFXL versus AFXL in a series of treatments over time.Materials and Methods: In this prospective, proof of principle, single-case study, the safety, tolerability and efficacy of the laser systems were assessed via histopathology and clinical evaluations including photographs. Optical biopsies by means of multiphoton tomography (MPT) were used to evaluate the induction of collagen and elastin remodeling.Results: Treatments by both NAFXL and AFXL were well tolerated. The NAFXL system was found to be less painful and resulted in a shorter down- and healing times. MPT findings showed the superior capability of the AFXL procedure to induce collagen; on the other hand, elastin induction was more pronounced after NAFXL treatments.Conclusions: While NAFXL is as effective and safe as the traditional AFXL, it is better tolerated and has a shorter downtime. Serial optical biopsies over time over time can be a useful tool to assess the induction of collagen and elastin remodeling in the human skin.

Effect of high flow arteriovenous fistula on cardiac function in hemodialysis patients.

BACKGROUND: Vascular access for hemodialysis (HD) with an inappropriately high flow may underlie the onset of high output heart failure (HOHF).The aim of this study was to determine the prevalence of high flow access (HFA) in chronic HD patients, and to determine its effects on cardiac functions. METHODS: This cross sectional study was conducted on 100 chronic hemodialysis patients through arteriovenous fistula (AVF). The study cohort was subdivided into 2 groups based on AVF flow: Group A (Non-HFA group with Qa < 2000 ml/min), and Group B (HFA group with Qa ≥ 2000 ml/min). AVF flow (Qa) was assessed using Color Doppler ultrasonography. Transthoracic echocardiography was performed for all patients to assess cardiac dimensions and functions. RESULTS: Prevalence of HFA among study population was 24%. Mean AVF Qa was 958.63 ±â€¯487.35 and 3430.13 ±â€¯1256.28 ml/min, for group A and B respectively. The HFA group demonstrated a significant dilatation in LV dimensions and volumes and significantly larger LA volume as compared to non-HFA group. A significantly lower LV ejection fraction [EF] was also observed in group B with a mean value of 57.32 ±â€¯6.19% versus 62.90 ±â€¯5.76%. A significant association between HFA group and high Qa/cardiac output (CO) ratio (≥20%) was also observed. CONCLUSION: HFA is a prevalent hemodialysis vascular access problem. HFA was associated with dilated LV dimensions, impaired LV systolic function. High Qa/CO ratio (≥20%) was an independent predictor of high output heart failure (HOHF) in our study population.

Characterizing Focused Attention and Working Memory Using EEG.

Detecting the cognitive profiles of learners is an important step towards personalized and adaptive learning. Electroencephalograms (EEG) have been used to detect the subject's emotional and cognitive states. In this paper, an approach for detecting two cognitive skills, focused attention and working memory, using EEG signals is proposed. The proposed approach consists of the following main steps: first, subjects undergo a scientifically-validated cognitive assessment test that stimulates and measures their full cognitive profile while putting on a 14-channel wearable EEG headset. Second, the scores of focused attention and working memory are extracted and encoded for a classification problem. Third, the collected EEG data are analyzed and a total of 280 time- and frequency-domain features are extracted. Fourth, several classifiers were trained to correctly classify and predict three levels (low, average, and high) of the two cognitive skills. The classification accuracies that were obtained on 86 subjects were 84% and 81% for the focused attention and working memory, respectively. In comparison with similar approaches, the obtained results indicate the generalizability and suitability of the proposed approach for the detection of these two skills. Thus, the presented approach can be used as a step towards adaptive learning where real-time adaptation is to be done according to the predicted levels of the measured cognitive skills.

Hyperinsulinemic Normoglycemia during Cardiac Surgery Reduces a Composite of 30-day Mortality and Serious In-hospital Complications: A Randomized Clinical Trial.

BACKGROUND: Hyperinsulinemic normoglycemia augments myocardial glucose uptake and utilization. We tested the hypothesis that hyperinsulinemic normoglycemia reduces 30-day mortality and morbidity after cardiac surgery. METHODS: This dual-center, parallel-group, superiority trial randomized cardiac surgical patients between August 2007 and March 2015 at the Cleveland Clinic, Cleveland, Ohio, and Royal Victoria Hospital, Montreal, Canada, to intraoperative glycemic management with (1) hyperinsulinemic normoglycemia, a fixed high-dose insulin and concomitant variable glucose infusion titrated to glucose concentrations of 80 to 110 mg · dl; or (2) standard glycemic management, low-dose insulin infusion targeting glucose greater than 150 mg · dl. The primary outcome was a composite of 30-day mortality, mechanical circulatory support, infection, renal or neurologic morbidity. Interim analyses were planned at each 12.5% enrollment of a maximum 2,790 patients. RESULTS: At the third interim analysis (n = 1,439; hyperinsulinemic normoglycemia, 709, standard glycemic management, 730; 52% of planned maximum), the efficacy boundary was crossed and study stopped per protocol. Time-weighted average glucose concentration (means ± SDs) with hyperinsulinemic normoglycemia was 108 ± 20 versus 150 ± 33 mg · dl with standard glycemic management, P < 0.001. At least one component of the composite outcome occurred in 49 (6.9%) patients receiving hyperinsulinemic normoglycemia versus 82 (11.2%) receiving standard glucose management (P < efficacy boundary 0.0085); estimated relative risk (95% interim-adjusted CI) 0.62 (0.39 to 0.97), P = 0.0043. There was a treatment-by-site interaction (P = 0.063); relative risk for the composite outcome was 0.49 (0.26 to 0.91, P = 0.0007, n = 921) at Royal Victoria Hospital, but 0.96 (0.41 to 2.24, P = 0.89, n = 518) at the Cleveland Clinic. Severe hypoglycemia (less than 40 mg · dl) occurred in 6 (0.9%) patients. CONCLUSIONS: Intraoperative hyperinsulinemic normoglycemia reduced mortality and morbidity after cardiac surgery. Providing exogenous glucose while targeting normoglycemia may be preferable to simply normalizing glucose concentrations.

Relationship of serum haemojuvelin and hepcidin levels with iron level and erythropoietin requirement in prevalent hepatitis C virus positive haemodialysis patients.

AIM: Iron overload is frequently reported in haemodialysis (HD) patients particularly those with chronic hepatitis C virus (HCV) infection. Soluble haemojuvelin (sHJV) has recently emerged as one of the significant regulators of iron homeostasis and hepcidin expression. The aim of the present study was to evaluate the potential associations of sHJV and hepcidin with inflammation, iron parameters and erythropoietin requirement in prevalent HD patients with HCV. METHODS: Serum sHJV and hepcidin were measured in 60 prevalent HD patients with [group I (n = 30)] and without [group II (n = 30)] HCV, and controls (n = 30) by enzyme-linked immunosorbent assay. Parameters related to anaemia, iron metabolism, inflammation, sHJV and hepcidin were measured. RESULTS: Serum hepcidin in HCV positive versus negative groups was 89.40 ± 46.08 ng/mL and 224.1 ± 72.36 ng/mL, P = 0.000, respectively, while sHJV was 245 ± 1.338 ng/mL and 254 ± 0.762 ng/mL, P = 0.147, respectively in positive versus negative patients. In group I, hepcidin correlated with serum ferritin (r = -0.512 P = 0.005) and transferrin saturation (TSAT%) (r = 0.572, P = 0.000) and sHJV correlated with ferritin (r = 0.40, P 0.000), TSAT% (r = 0.450, P = 0.002) and a significant correlation also existed between sHJV and hepcidin (r = -0.259, P = 0.045). In the regression analysis, ferritin and TSAT% were able to predict sHJV; (standardized ß = 0.52, P 0.001) and (standardized ß = 0.48, P 0.010). Ferritin and sHJV were also able to predict hepcidin (standardized ß = 0.627, P = 0.006) and (standardized ß = 0.300, P = 0.007) in group I. CONCLUSION: Soluble haemojuvelin levels seem to be associated with iron overload parameters and hepcidin levels in HCV positive HD patients.

Value of immunohistochemical expression of podocalyxin in active lupus nephritis.

Podocalyxin is an electronegative sialoglycoprotein that prevents the podocyte foot process from collapsing. The aim of this study was to detect an association between the glomerular immunohistochemical (IHC) expression of podocalyxin and the degree of podocyte effacement detected by electron microscopy, and to evaluate the role of podocalyxin IHC expression as a novel marker for disease activity in lupus nephritis (LN). METHODS: Thirty-two renal biopsies of active lupus nephritis patients were studied. Clinical assessment by the systemic lupus activity measure (SLAM-R) score and laboratory data were included [serum creatinine, 24-h urinary protein, antinuclear antibodies (ANA), anti-double-strand DNA antibodies (anti-dsDNA), C3 and C4]. Light (L/M) and electron microscopic (E/M) examination was conducted. Podocyte loss was evaluated by immunohistochemistry with monoclonal anti-podocalyxin antibodies by means of a semiquantitative score that was graded from 0 to 4+ according to the percentage of glomerular involvement. RESULTS: 22 cases (68.8%) with LN class IV, 6 (18.8%) with class III and 4 (12.5%) with class V. The mean age was (25.41±10.13) years. There was a significant negative correlation between IHC podocalyxin score and LN class, and NIH activity parameters such as leukocyte infiltration, endocapillary proliferation, fibrinoid necrosis and cellular crescent and disease activity index but not chronicity index. There was a highly significant negative correlation between IHC podocalyxin and podocyte effacement by E/M (rs=-0.903, P=0.000), and E/M immune deposits (r=-0.53, P=0.001), and a significant association with degree of proteinuria, ANA and SLAM score (P<0.05). CONCLUSIONS: Podocyte loss indicated by podocalyxin immunohistochemical expression reflects the degree of activity and severity of LN and the degree of podocyte effacement by E/M.

Central obesity and risks of cardiovascular events and mortality in prevalent hemodialysis patients.

BACKGROUND: To date, no attempt has been made to assess the best anthropometric method for defining abdominal adiposity in hemodialysis (HD) patients or to determine whether the quantity of intra-abdominal fat relates to morbidity and mortality in that population. We aimed to describe the prevalence of central obesity in HD patients and to investigate the relationship between central obesity assessed by anthropometric variables, and composite outcomes, cardiovascular morbidity and mortality among HD patients and whether this parameter correlates with intra-abdominal fat assessed by computed tomography scan (CT scan). METHODS: The procedures followed were in accord with the ethical standards of the committee on human experimentation of our institution. Informed oral consent was obtained from all patients. This was a cross-sectional study of 120 prevalent HD patients. Anthropometric measurements including body mass index, conicity index (Ci), waist-hip ratio (WHR), waist circumference (WC), waist-to-height ratio (WHtR), and visceral adiposity index (VAI) were recorded. Visceral and subcutaneous abdominal fat were assessed by CT scan. Comorbidity was scored for both the Charlson comorbidity index (CCI) and Davies comorbidity index. RESULTS: Twenty-eight patients (23.3%) were centrally obese based on anthropometry. By linear regression analysis, Ci, WHR, and VAI were predictors of CT assessed central obesity; p 0.042, 0.001, and 0.010, respectively. On assessment of the relationship between the abdominal obesity and the comorbidity indices, there was a positive significant correlation between Ci and CCI (p 0.025) and Davies score (p 0.002) which are predictors of mortality. During the mean follow-up period (3.2 years), 56 patients reached the composite outcome; eight patients died and 48 experienced CV events. Central obesity measured by anthropometry was a predictor of composite outcomes, cardiovascular morbidity, and mortality in HD patients by regression analysis and cox regression model. Only WC and WHtR did not predict mortality. CONCLUSION: Ci, WHR, and VAI are cheap alternatives for accurate assessment of morbidity and mortality risk in centrally obese prevalent HD patients.

Laparoscopic Management of Interstitial Ectopic Using Simple and Safe Technique: Case Series and Review of Literature.

BACKGROUND AND OBJECTIVE: To determine the safety and sustainability of operative laparoscopy in surgical management of cornual and interstitial ectopic pregnancy using a simple and practical method. DESIGN: Case series of five consecutive cases. SETTING: Endoscopy unit in Alexandria University Hospital and Alexandria New Medical Center. PATIENTS: Between July 2013 and May 2015, five women with interstitial and cornual ectopic pregnancies were admitted for laparoscopic surgical treatment. METHODS: Full medical and surgical histories were taken. We explained all alternatives for both partners before informed. Patients underwent laparoscopy for management of the corneal ectopic. All surgeries were done by the same surgeon (T.S.) with different assistants. We gave different uterotonics drugs to devascularize the uterus. Two or more devascularization sutures were done on each end of the corneal ectopic. We used monopolar and bipolar electrocoagulation when indicated. We did linear cut of the interstitial ectopic with evacuation of the fetus and placental tissues. Extraction of the conceptus was performed through 10 mm port. Follow-up of the beta-hCG was done weekly till negative results were obtained. RESULTS: The devascularization sutures together with uterotonics make the surgical treatment of interstitial ectopic easy and safe. This simple technique minimizes blood loss and decreases necrosis that follows excessive use of diathermy. This was demonstrated successfully in different types of interstitial ectopic. We did not remove any part of the uterus during surgery. Clinical criteria of the study cases were discussed. Type, size, blood loss and complications, and duration of the surgery were documented. CONCLUSION: Operative laparoscopy using sutures and uterotonics is safe and sustainable approach in treatment of interstitial ectopic pregnancy.

Role of Laparoscopic Exploration Under Local Anesthesia in the Management of Hemodynamically Stable Patients with Penetrating Abdominal Injury.

BACKGROUND: In many trauma centers there is an ongoing controversy over the way of managing patients with penetrating abdominal injuries. This study was constructed to evaluate the role of diagnostic laparoscopy performed with local anesthesia for the management of penetrating abdominal injury. PATIENTS AND METHODS: Thirty hemodynamically stable patients with a penetrating stab wound in the anterior abdominal wall were included in this study after consent was obtained. Laparoscopic explorations were done with the patient having local anesthesia. If there was bleeding or intestinal content in the peritoneal cavity or visible injury to any abdominal organ, the procedure was converted to open exploration. If the peritoneal cavities showed no fluid and there was no injury to the abdominal viscera, the patient was followed up for the next 72 hours. Continuous variables were expressed as mean and standard deviation values. Categorical variables were expressed as frequencies and percentages. Student's t test was used to assess the statistical significance of the difference between the two study groups' means. Fisher's exact test was used to examine the relationship between categorical variables. A significance level of P < .05 was used in all tests. All statistical procedures were carried out using SPSS version 20 for Windows software (IBM, Armonk, NY). RESULTS: From the total of 30 patients who underwent laparoscopic exploration, 13 patients (43.3%) needed open exploration: 11 cases had intrabdominal organ injuries that needed laparotomy, 1 case had intraperitoneal blood collection where the only source of blood was the anterior abdominal wall wound, and 1 case had acute abdominal pain after 48 hours of negative laparoscopic exploration, in which an intestinal tear was found upon re-exploration. For the other 17 (56.7%) cases, 3 cases had no peritoneal penetration, whereas 14 cases had peritoneal penetration without any internal organ injuries, and these patients were followed up and discharged after 2-3 days. CONCLUSIONS: Laparoscopy performed with the patient having local anesthesia is an accurate diagnostic tool in the management of patients with an equivocal penetrating stab wound in the abdominal wall and can reduce the number of patients with negative open exploration.

Zeroing in on the cause of your patient's facial pain.

The overlapping characteristics of facial pain can make it difficult to pinpoint the cause. This article, with a handy at-a-glance table, can help.

Ionic bases for electrical remodeling of the canine cardiac ventricle.

Emerging evidence suggests that ventricular electrical remodeling (VER) is triggered by regional myocardial strain via mechanoelectrical feedback mechanisms; however, the ionic mechanisms underlying strain-induced VER are poorly understood. To determine its ionic basis, VER induced by altered electrical activation in dogs undergoing left ventricular pacing (n = 6) were compared with unpaced controls (n = 4). Action potential (AP) durations (APDs), ionic currents, and Ca(2+) transients were measured from canine epicardial myocytes isolated from early-activated (low strain) and late-activated (high strain) left ventricular regions. VER in the early-activated region was characterized by minimal APD prolongation, but marked attenuation of the AP phase 1 notch attributed to reduced transient outward K(+) current. In contrast, VER in the late-activated region was characterized by significant APD prolongation. Despite marked APD prolongation, there was surprisingly minimal change in ion channel densities but a twofold increase in diastolic Ca(2+). Computer simulations demonstrated that changes in sarcolemmal ion channel density could only account for attenuation of the AP notch observed in the early-activated region but failed to account for APD remodeling in the late-activated region. Furthermore, these simulations identified that cytosolic Ca(2+) accounted for APD prolongation in the late-activated region by enhancing forward-mode Na(+)/Ca(2+) exchanger activity, corroborated by increased Na(+)/Ca(2+) exchanger protein expression. Finally, assessment of skinned fibers after VER identified altered myofilament Ca(2+) sensitivity in late-activated regions to be associated with increased diastolic levels of Ca(2+). In conclusion, we identified two distinct ionic mechanisms that underlie VER: 1) strain-independent changes in early-activated regions due to remodeling of sarcolemmal ion channels with no changes in Ca(2+) handling and 2) a novel and unexpected mechanism for strain-induced VER in late-activated regions in the canine arising from remodeling of sarcomeric Ca(2+) handling rather than sarcolemmal ion channels.

Transmural dispersion of repolarization as a preclinical marker of drug-induced proarrhythmia.

Torsade de Pointes (TdP) proarrhythmia is a major complication of therapeutic drugs that block the delayed rectifier current. QT interval prolongation, the principal marker used to screen drugs for proarrhythmia, is both insensitive and nonspecific. Consequently, better screening methods are needed. Drug-induced transmural dispersion of repolarization (TDR) is mechanistically linked to TdP. Therefore, we hypothesized that drug-induced enhancement of TDR is more predictive of proarrhythmia than QT interval. High-resolution transmural optical action potential mapping was performed in canine wedge preparations (n = 19) at baseline and after perfusion with 4 different QT prolonging drugs at clinically relevant concentrations. Two proarrhythmic drugs in patients (bepridil and E4031) were compared with 2 nonproarrhythmic drugs (risperidone and verapamil). Both groups prolonged the QT (all P < 0.02), least with the proarrhythmic drug bepridil, reaffirming that QT is a poor predictor of TdP. In contrast, TDR was enhanced only by proarrhythmic drugs (P < 0.03). Increased TDR was due to a preferential prolongation of midmyocardial cell, relative to epicardial cell, APD, whereas nonproarrhythmic drugs similarly prolonged both cell types. In contrast to QT prolongation, augmentation of TDR was induced by proarrhythmic but not nonproarrhythmic drugs, suggesting TDR is a superior preclinical marker of proarrhythmic risk during drug development.

Effects of advanced selection methods on sperm quality and ART outcome: a systematic review.

BACKGROUND: Current routine semen preparation techniques do not inclusively target all intrinsic sperm characteristics that may impact the fertilization potential. In order to address these characteristics, several methods have been recently developed and applied to sperm selection. The objective of this study was to systematically review the literature describing these advanced sperm selection methods focusing on their anticipated benefits on sperm quality and assisted reproductive technique (ART) outcome. METHODS: Systematic literature review was conducted by means of a Medline literature search. Sperm quality parameters assessed included: motility, morphology, viability, DNA integrity, apoptosis and maturity. ART outcomes assessed included: fertilization, embryo quality, pregnancy, abortion and live birth rates. RESULTS: A total of 44 studies were identified describing four advanced sperm selection methods based on: (i) surface charge (electrophoresis and zeta potential), (ii) apoptosis (magnetic cell sorting and glass wool), (iii) membrane maturity (hyaluronic acid binding) and (iv) ultramorphology (high magnification). Selection of high-quality sperm including improvements in DNA integrity, resulted from the application of these methods. Fertilization and pregnancy rates showed improvement following some of the advanced sperm selection techniques. CONCLUSIONS: While some of the advanced sperm selection methods are of value in specific clinical ART settings, others are in need of further evaluation. More clinical studies on safety and efficacy are needed before the implementation of advanced sperm selection methods could be universally recommended in ART.

Enhanced dispersion of repolarization explains increased arrhythmogenesis in severe versus therapeutic hypothermia.

BACKGROUND: Hypothermia is proarrhythmic, and, as the use of therapeutic hypothermia (TH) increases, it is critically important to understand the electrophysiological effects of hypothermia on cardiac myocytes and arrhythmia substrates. We tested the hypothesis that hypothermia-enhanced transmural dispersion of repolarization (DOR) is a mechanism of arrhythmogenesis in hypothermia. In addition, we investigated whether the degree of hypothermia, the rate of temperature change, and cooling versus rewarming would alter hypothermia-induced arrhythmia substrates. METHODS AND RESULTS: Optical action potentials were recorded from cells spanning the transmural wall of canine left ventricular wedge preparations at baseline (36°C), during cooling and during rewarming. Electrophysiological parameters were examined while varying the depth of hypothermia. On cooling to 26°C, DOR increased from 26±4 ms to 93±18 ms (P=0.021); conduction velocity decreased from 35±5 cm/s to 22±5 cm/s (P=0.010). On rewarming to 36°C, DOR remained prolonged, whereas conduction velocity returned to baseline. Conduction block and reentry was observed in all severe hypothermia preparations. Ventricular fibrillation/ventricular tachycardia was seen more during rewarming (4/5) versus cooling (2/6). In TH (n=7), cooling to 32°C mildly increased DOR (31±6 to 50±9, P=0.012), with return to baseline on rewarming and was associated with decreased arrhythmia susceptibility. Increased rate of cooling did not further enhance DOR or arrhythmogenesis. CONCLUSIONS: Hypothermia amplifies DOR and is a mechanism for arrhythmogenesis. DOR is directly dependent on the depth of cooling and rewarming. This provides insight into the clinical observation of a low incidence of arrhythmias in TH and has implications for protocols for the clinical application of TH.

Assessment of male serum anti-Mullerian hormone as a marker of spermatogenesis and ICSI outcome.

OBJECTIVE: To assess serum anti-Mullerian hormone (AMH) as a marker of spermatogenesis among fertile and infertile males, as well as its relation to ICSI outcome. METHODS: A total of 77 male partners of infertile couples seeking infertility treatment were recruited for this study. They were classified according to the WHO criteria of semen analysis into three groups; azospermia, oligospermia, and normal. All participating patients had a serum assay of the level of AMH. Thirty-three couples out of the previously mentioned 77 couples underwent controlled ovarian stimulation and ICSI. RESULTS: There were 41 patients with azospermia, 14 patients with oligospermia, and 22 patients with normal count. There was no significant difference among the three groups regarding the AMH levels. There was no significant correlation between the AMH levels from all patients and the sperm concentration (rho = 0.03, p = 0.82). Among patients who underwent ICSI, there was no significant correlation of the AMH with the age, sperm concentration, fertilisation percent or number of embryos. The age of male partners was significantly correlated with sperm concentration, fertilisation percent and the total number of embryos. In the logistic regression model used, serum AMH had no significant relation to clinical pregnancy. CONCLUSION: Male serum AMH levels are not indicative of spermatogenesis and cannot differentiate between fertile and infertile males. Serum AMH levels were not predictive of ICSI outcome as well.

Implication of apoptosis in sperm cryoinjury.

Apoptosis is an ongoing physiological phenomenon that has been documented to play a role in male infertility, if deregulated. Caspase activation, externalization of phosphatidylserine, alteration of mitochondrial membrane potential and DNA fragmentation are markers of apoptosis found in ejaculated human spermatozoa. These markers appear in excess in subfertile men and functionally incompetent spermatozoa. Sperm cryopreservation is a widely used procedure in the context of assisted reproductive techniques. Cryopreservation and thawing is a procedure that inflicts irreversible injury on human spermatozoa. The damage is manifested by a decrease in recovery of viable spermatozoa with optimum fertilization potential. This review describes the implication of apoptosis as one of the possible mechanisms involved in sperm cryoinjury. Evidence shows significant increase in some apoptosis markers following cryopreservation and thawing. On the other hand, the increase in sperm DNA fragmentation following cryopreservation and thawing requires further investigation. Specific technical measures should be applied to minimize the induction of apoptosis in human spermatozoa during cryopreservation and thawing. These include standardization of freezing protocols and cryoprotectant use. Selection of non-apoptotic spermatozoa may also prove to be of benefit.