Disruptions in reproductive health, sex hormonal profiles, and hypothalamic hormone receptors content in females of the C58/J mouse model of autism.

Autism Spectrum Disorder (ASD) is characterized by differences in social communication and interaction, as well as areas of focused interests and/or repetitive behaviors. Recent studies have highlighted a higher prevalence of endocrine and reproductive disturbances among females on the autism spectrum, hinting at potential disruptions within the hypothalamus-pituitary-ovary (HPO) axis. This research aims to explore the reproductive health disparities in ASD using an animal model of autism, the C58/J inbred mouse strain, with a focus on reproductive performance and hormonal profiles compared to the C57BL/6J control strain. Our findings revealed that the estrous cycle in C58/J females is disrupted, as evidenced by a lower frequency of complete cycles and a lack of cyclical release of estradiol and progesterone compared to control mice. C58/J females also exhibited poor performance in several reproductive parameters, including reproductive lifespan and fertility index. Furthermore, estrogen receptor alpha content showed a marked decrease in the hypothalamus of C58/J mice. These alterations in the estrous cycle, hormonal imbalances, and reduced reproductive function imply dysregulation in the HPO axis. Additionally, our in-silico study identified a group of genes involved in infertility carrying single-nucleotide polymorphisms (SNPs) in the C58/J strain, which also have human orthologs associated with autism. These findings could offer valuable insights into the molecular underpinnings of neuroendocrine axis disruption and reproductive issues observed in ASD.

Improved Feedback Quantizer with Discrete Space Vector.

The use of advanced modulation and control schemes for power converters, such as a Feedback Quantizer and Predictive Control, is widely studied in the literature. This work focuses on improving the closed-loop modulation scheme called Feedback Quantizer, which is applied to a three-phase voltage source inverter. This scheme has the natural behavior of mitigating harmonics at low frequencies, which are detrimental to electrical equipment such as transformers. This modulation scheme also provides good tracking for the voltage reference at the fundamental frequency. On the other hand, the disadvantage of this scheme is that it has a variable switching frequency, creating a harmonic spectrum in frequency dispersion, and it also needs a small sampling time to obtain good results. The proposed scheme to improve the modulation scheme is based on a Discrete Space Vector with virtual vectors to obtain a better approximation of the optimal vectors for use in the algorithm. The proposal improves the conventional scheme at a high sampling time (200 µs), obtaining a THD less than 2% in the load current, decreases the noise created by the conventional scheme, and provides a fixed switching frequency. Experimental tests demonstrate the correct operation of the proposed scheme.

High Pulsed Voltage Alkaline Electrolysis for Water Splitting.

Pulsed electrolysis has become a promising research topic in recent decades due to advances in solid-state semiconductor devices. These technologies have enabled the design and construction of simpler, more efficient, and less costly high-voltage and high-frequency power converters. In this paper, we study high-voltage pulsed electrolysis considering variations in both power converter parameters and cell configuration. Experimental results are obtained for frequency variations ranging from 10 Hz to 1 MHz, voltage changes from 2 V to 500 V, and electrode separations from 0.1 to 2 mm. The results demonstrate that pulsed plasmolysis is a promising method for decomposing water for hydrogen production.

Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence.

The B-cell lymphoma 2 (Bcl-2) family of proteins is the main regulator of apoptosis. However, multiple emerging evidence has revealed that Bcl-2 family proteins are also involved in cellular senescence. On the one hand, the different expression of these proteins determines the entry into senescence. On the other hand, entry into senescence modulates the expression of these proteins, generally conferring resistance to apoptosis. With some exceptions, senescent cells are characterized by the upregulation of antiapoptotic proteins and downregulation of proapoptotic proteins. Under physiological conditions, freshly formed tetraploid cells die by apoptosis due to the tetraploidy checkpoint. However, suppression of Bcl-2 associated x protein (Bax), as well as overexpression of Bcl-2, favors the appearance and survival of tetraploid cells. Furthermore, it is noteworthy that our laboratory has shown that the joint absence of Bax and Bcl-2 antagonist/killer (Bak) favors the entry into senescence of tetraploid cells. Certain microtubule inhibitory chemotherapies, such as taxanes and vinca alkaloids, induce the generation of tetraploid cells. Moreover, the combined use of inhibitors of antiapoptotic proteins of the Bcl-2 family with microtubule inhibitors increases their efficacy. In this review, we aim to shed light on the involvement of the Bcl-2 family of proteins in the senescence program activated after tetraploidization and the possibility of using this knowledge to create a new therapeutic strategy targeting cancer cells.

Benefits of the Non-Steroidal Mineralocorticoid Receptor Antagonist Finerenone in Metabolic Syndrome-Related Heart Failure with Preserved Ejection Fraction.

The mineralocorticoid receptor (MR) plays an important role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Antagonizing the overactivation of the MR with MR antagonists (MRA) is a therapeutic option, but their use in patients with CKD is limited due to the associated risk of hyperkalemia. Finerenone is a non-steroidal MRA associated with an improved benefit-risk profile in comparison to steroidal MRAs. In this study, we decided to test whether finerenone improves renal and cardiac function in male hypertensive and diabetic ZSF1 rats as an established preclinical HFpEF model. Finerenone was administered at 10 mg/kg/day for 12 weeks. Cardiac function/hemodynamics were assessed in vivo. ZSF1 rats showed classical signs of CKD with increased BUN, UACR, hypertrophy, and fibrosis of the kidney together with characteristic signs of HFpEF including cardiac fibrosis, diastolic dysfunction, and decreased cardiac perfusion. Finerenone treatment did not impact kidney function but reduced renal hypertrophy and cardiac fibrosis. Interestingly, finerenone ameliorated diastolic dysfunction and cardiac perfusion in ZSF1 rats. In summary, we show for the first time that non-steroidal MR antagonism by finerenone attenuates cardiac diastolic dysfunction and improves cardiac perfusion in a preclinical HFpEF model. These cardiac benefits were found to be largely independent of renal benefits.

Biglycan Is a Novel Mineralocorticoid Receptor Target Involved in Aldosterone/Salt-Induced Glomerular Injury.

The beneficial effects of mineralocorticoid receptor (MR) antagonists (MRAs) for various kidney diseases are established. However, the underlying mechanisms of kidney injury induced by MR activation remain to be elucidated. We recently reported aldosterone-induced enhancement of proteoglycan expression in mitral valve interstitial cells and its association with fibromyxomatous valvular disorder. As the expression of certain proteoglycans is elevated in several kidney diseases, we hypothesized that proteoglycans mediate kidney injury in the context of aldosterone/MR pathway activation. We evaluated the proteoglycan expression and tissue injury in the kidney and isolated glomeruli of uninephrectomy/aldosterone/salt (NAS) mice. The MRA eplerenone was administered to assess the role of the MR pathway. We investigated the direct effects of biglycan, one of the proteoglycans, on macrophages using isolated macrophages. The kidney samples from NAS-treated mice showed enhanced fibrosis and increased expression of biglycan accompanying glomerular macrophage infiltration and enhanced expression of TNF-α, iNOS, Nox2, CCL3 (C-C motif chemokine ligand 3), and phosphorylated NF-κB. Eplerenone blunted these changes. Purified biglycan stimulated macrophages to express TNF-α, iNOS, Nox2, and CCL3. This was prevented by a toll-like receptor 4 (TLR4) or NF-κB inhibitor, indicating that biglycan stimulation is dependent on the TLR4/NF-κB pathway. We identified the proteoglycan biglycan as a novel target of MR involved in MR-induced glomerular injury and macrophage infiltration via a biglycan/TLR4/NF-κB/CCL3 cascade.

Insights into functional mitral regurgitation using transillumination rendering.

Secondary mitral regurgitation has been originally explained by tethering of the structurally normal mitral leaflets or by mitral annular dilation after atrial remodeling. Advances in echocardiography have provided more insights into functional anatomy of the mitral valve leaflets as active participants in this entity.

Manchester Arena Attack: management of paediatric penetrating brain injuries.

PURPOSE: The Manchester Arena bombing on 22 May 2017 resulted in 22 deaths and over 160 casualties requiring medical attention. Given the threat of modern- era terrorist attacks in civilian environments, it is important that we are able to anticipate and appropriately manage neurological injuries associated with these events. This article describes our experience of managing paediatric neurosurgical blast injuries, from initial triage and operative management to longer-term considerations. MATERIALS AND METHODS: Case study and literature review. RESULTS: Paediatric traumatic and penetrating brain injury patients often make a good neurological recovery despite low GCS at time of injury; this should be accounted for during triage and operative decision making in major trauma, mass casualty events. Conservative management of retained shrapnel is advocated in view of low long-term infection rates with retained shrapnel and worsened neurological outcome with shrapnel retrieval. All penetrating brain injuries should receive a prolonged course of broad-spectrum antibiotics and undergo long term follow-up imaging to monitor for the development of cerebral abscesses. MRI should never be utilised in penetrating brain injury cases, even in the absence of macroscopically visible fragments, due to the effect of MRI ferromagnetic field torque on shrapnel fragments. Anti-epileptic drugs should only be prescribed for the initial seven days after injury, as continuing beyond this does not incur any benefit in the reduction of long term post-traumatic epilepsy. CONCLUSION: All receiving neurosurgical units should become familiar with optimum management of these thankfully rare, but complex injuries from their initial presentation to long term follow up considerations. All neurosurgical units should have well-rehearsed local plans to follow in the event of such incidents, ensuring timely deliverance of appropriate neurosurgical care in such extreme settings.

Dehiscence and prolonged storage of 'Kerman' Pistachios: Effects on morphometry and nutraceutical value.

'Kerman' pistachios (KP; Pistacia vera L.) are an important crop for several countries but their commercial value is diminished by their shell dehiscence status and prolonged storage in popular marketplaces. The aim was to evaluate the independent/synergistic effect of prolonged storage (1-4 year) and dehiscence status (split/unsplit) on KP's morphometry and chemical composition. Whole nut's and kernel's length, width, thickness, surface area, and volume were more affected by dehiscence (split > unsplit; p ≤ 0.01) than storage time; Kernel's mass, macronutrient composition and tocopherols (T)/tocotrienols (T3) were not much affected by dehiscence but time-trend correlations were observed with macronutrient composition (split/unsplit; ρ = - 0.57-0.42) and T + T3 (unsplit; ρ = 0.81). Specific/total fatty acids were affected by a complex dehiscence × storage time interaction, and they linearly correlated with certain morphometric characteristics (r ≥ 0.6). Shell dehiscence status more than prolonged storage substantially modifies KP's quality.

Unsupervised clustering for phenotypic stratification of clinical, demographic, and stress attributes of cardiac risk in patients with nonischemic exercise stress echocardiography.

INTRODUCTION AND AIM: Patients undergoing exercise echocardiography with no evidence of myocardial ischemia are considered a low-risk group; however, this group is likely heterogeneous in terms of short-term adverse events and subsequent cardiac testing. We hypothesized that unsupervised cluster modeling using clinical and stress characteristics can detect heterogeneity in cardiovascular risk and need for subsequent cardiac testing among these patients. METHODS: We retrospectively studied 445 patients who had exercise echocardiography results negative for myocardial ischemia. All patients were followed for adverse cardiovascular events, subsequent cardiac testing, and nonacute coronary syndrome (ACS) revascularization. The heterogeneity of the study subjects was tested using computational clustering, an exploratory statistical method designed to uncover invisible natural groups within data. Clinical and stress predictors of adverse events were extracted and used to construct 3 unsupervised cluster models: clinical, stress, and combined. The study population was split into training (357 patients) and testing sets (88 patients). RESULTS: In the training set, the clinical, stress, and combined cluster models yielded 5, 4, and 3 clusters, respectively. Each model had 1 high-risk and 1 low-risk cluster while other clusters were intermediate. The combined model showed a better predictive ability compared to the clinical or stress models alone. The need for future testing mirrored the pattern of adverse cardiovascular events. A risk score derived from the combined cluster model predicted end points with acceptable accuracy. The patterns of risk and the calculated risk scores were preserved in the testing set. CONCLUSIONS: Patients with no evidence of ischemia on exercise stress echocardiography represent a heterogeneous group. Cluster-based modeling using combined clinical and stress characteristics can expose this heterogeneity. The findings can help better risk-stratify this group of patients and aid cost-effective healthcare utilization toward better diagnostics and therapeutics.

Obtaining glycoconjugates of marine origin via Maillard reaction and their cytotoxic effect: an alternative for the use of animal byproducts.

BACKGROUND: Protein glycation by Maillard reaction is commonly used to improve the functional and bioactive properties of food proteins. It is also known that this glycation method can be accelerated by heat without the need for chemical reagents that could be harmful to health. In this study, glycoconjugates were obtained from a mixture of connective tissue proteins (CTP) from jumbo squid (Dosidicus gigas) and two different sugars, dextran (DEX; 10 kDa) and glucose (GLU), using protein-to-carbohydrate ratios of 1:2 and 1:3, in solution at 50 °C for 6 h. The glycation products were characterized by means of their physicochemical properties and cytotoxic effect. RESULTS: The intensity of the browning measured at A420nm and A294nm in glycoconjugates showed no significant difference (P < 0.05). CTP-DEX (1:2) and CTP-DEX (1:3) were those products with the greatest fluorescence related to the intermediate stage in the Maillard reaction, and also with the highest degree of glycation, which was confirmed using o-phthaldialdehyde assay and Fourier transform infrared analysis. The values of cellular viability for CTP-GLU (1:3), CTP-DEX (1:2, 1:3) as well as CTP (0, 6 h) were around 92-103%. CONCLUSIONS: The operational parameters used in the glycation process achieved the formation of glycoconjugates from proteins of D. gigas, showing no cytotoxic effect on the HaCaT cell line. This research proposes an alternative for the modification of proteins and opens the way to future investigations regarding the bioactivity of these macromolecules to have applications for the use of byproducts in food science and technology. © 2020 Society of Chemical Industry.

Surgery for epilepsy.

BACKGROUND: This is an updated version of the original Cochrane review, published in 2015.Focal epilepsies are caused by a malfunction of nerve cells localised in one part of one cerebral hemisphere. In studies, estimates of the number of individuals with focal epilepsy who do not become seizure-free despite optimal drug therapy vary between at least 20% and up to 70%. If the epileptogenic zone can be located, surgical resection offers the chance of a cure with a corresponding increase in quality of life. OBJECTIVES: The primary objective is to assess the overall outcome of epilepsy surgery according to evidence from randomised controlled trials.Secondary objectives are to assess the overall outcome of epilepsy surgery according to non-randomised evidence, and to identify the factors that correlate with remission of seizures postoperatively. SEARCH METHODS: For the latest update, we searched the following databases on 11 March 2019: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to March 08, 2019), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs) that included at least 30 participants in a well-defined population (age, sex, seizure type/frequency, duration of epilepsy, aetiology, magnetic resonance imaging (MRI) diagnosis, surgical findings), with an MRI performed in at least 90% of cases and an expected duration of follow-up of at least one year, and reporting an outcome related to postoperative seizure control. Cohort studies or case series were included in the previous version of this review. DATA COLLECTION AND ANALYSIS: Three groups of two review authors independently screened all references for eligibility, assessed study quality and risk of bias, and extracted data. Outcomes were proportions of participants achieving a good outcome according to the presence or absence of each prognostic factor of interest. We intended to combine data with risk ratios (RRs) and 95% confidence intervals (95% CIs). MAIN RESULTS: We identified 182 studies with a total of 16,855 included participants investigating outcomes of surgery for epilepsy. Nine studies were RCTs (including two that randomised participants to surgery or medical treatment (99 participants included in the two trials received medical treatment)). Risk of bias in these RCTs was unclear or high. Most of the remaining 173 non-randomised studies followed a retrospective design. We assessed study quality using the Effective Public Health Practice Project (EPHPP) tool and determined that most studies provided moderate or weak evidence. For 29 studies reporting multivariate analyses, we used the Quality in Prognostic Studies (QUIPS) tool and determined that very few studies were at low risk of bias across domains.In terms of freedom from seizures, two RCTs found surgery (n = 97) to be superior to medical treatment (n = 99); four found no statistically significant differences between anterior temporal lobectomy (ATL) with or without corpus callosotomy (n = 60), between subtemporal or transsylvian approach to selective amygdalohippocampectomy (SAH) (n = 47); between ATL, SAH and parahippocampectomy (n = 43) or between 2.5 cm and 3.5 cm ATL resection (n = 207). One RCT found total hippocampectomy to be superior to partial hippocampectomy (n = 70) and one found ATL to be superior to stereotactic radiosurgery (n = 58); and another provided data to show that for Lennox-Gastaut syndrome, no significant differences in seizure outcomes were evident between those treated with resection of the epileptogenic zone and those treated with resection of the epileptogenic zone plus corpus callosotomy (n = 43). We judged evidence from the nine RCTs to be of moderate to very low quality due to lack of information reported about the randomised trial design and the restricted study populations.Of the 16,756 participants included in this review who underwent a surgical procedure, 10,696 (64%) achieved a good outcome from surgery; this ranged across studies from 13.5% to 92.5%. Overall, we found the quality of data in relation to recording of adverse events to be very poor.In total, 120 studies examined between one and eight prognostic factors in univariate analysis. We found the following prognostic factors to be associated with a better post-surgical seizure outcome: abnormal pre-operative MRI, no use of intracranial monitoring, complete surgical resection, presence of mesial temporal sclerosis, concordance of pre-operative MRI and electroencephalography, history of febrile seizures, absence of focal cortical dysplasia/malformation of cortical development, presence of tumour, right-sided resection, and presence of unilateral interictal spikes. We found no evidence that history of head injury, presence of encephalomalacia, presence of vascular malformation, and presence of postoperative discharges were prognostic factors of outcome.Twenty-nine studies reported multi-variable models of prognostic factors, and showed that the direction of association of factors with outcomes was generally the same as that found in univariate analyses.We observed variability in many of our analyses, likely due to small study sizes with unbalanced group sizes and variation in the definition of seizure outcome, the definition of prognostic factors, and the influence of the site of surgery AUTHORS' CONCLUSIONS: Study design issues and limited information presented in the included studies mean that our results provide limited evidence to aid patient selection for surgery and prediction of likely surgical outcomes. Future research should be of high quality, follow a prospective design, be appropriately powered, and focus on specific issues related to diagnostic tools, the site-specific surgical approach, and other issues such as extent of resection. Researchers should investigate prognostic factors related to the outcome of surgery via multi-variable statistical regression modelling, where variables are selected for modelling according to clinical relevance, and all numerical results of the prognostic models are fully reported. Journal editors should not accept papers for which study authors did not record adverse events from a medical intervention. Researchers have achieved improvements in cancer care over the past three to four decades by answering well-defined questions through the conduct of focused RCTs in a step-wise fashion. The same approach to surgery for epilepsy is required.

Hormonal correlates of energetic condition in mantled howler monkeys.

Hormones have a key role in energy allocation, so their study allows understanding individual metabolic strategies. Because different hormones convey different information on the responses of individuals to energetic demands, a simultaneous analysis of variation in multiple hormones may offer a more reliable picture of metabolic strategies than single hormone assessments. In this study we focused on determining which factors were related to variation in fecal glucocorticoid and thyroid hormone metabolites in wild mantled howler monkeys (Alouatta palliata). Over 12months, we determined fecal glucocorticoid and thyroid hormone metabolite levels of 11 adults belonging to two groups, and examined the relationship between hormone metabolites and a variety of behavioral, physiological, and ecological factors (e.g., food intake, sex/reproductive state, activity, participation in agonistic interactions). We found that glucocorticoids were elevated in gestating and lactating females compared to males and cycling females, and were also higher when individuals were more active and participated in agonistic interactions. Thyroid hormone levels were also related to sex/reproductive state and activity, but were additionally positively related to fruit intake and negatively related to young leaf intake. Our study demonstrates that the non-invasive measurement of glucocorticoid and thyroid hormones of howler monkeys allows assessing different underlying physiological processes. By combining different biomarkers, which has seldom been done with wildlife, we could also parse the influence of psychological vs. metabolic challenges for individual energetic condition, which may be instrumental for deciding which factors should be accounted for when studying different hormone-behavior interactions.

Telemetric intra-cranial pressure monitoring: clinical and financial considerations.

Intracranial pressure (ICP) measurement is an important diagnostic tool in Neurosurgery. Until relatively recently, conventional monitoring has required that subjects be admitted to a hospital bed and the device is only able to be left in-situ for limited periods of time. We have evaluated a Telemetric ICP monitoring system that has been proven, by several other groups worldwide, to permit rapid, repeated and prolonged ICP measurement, in multiple environments. In our unit, 4 patients have been implanted to-date, between the ages of 4 and 16, manifesting a wide range of complex neurosurgical conditions. The sensors have been left in-situ for between 460 and 632 days. There have been no clinical complications and the system has been universally well tolerated. Clinical events, costs and patient experience were all assessed prior to and following implantation. Overall, there was a significant reduction in associated admissions (44.3%), imaging requirements (72.5%) and costs (50.0%). Subjective feedback from both the patients (where possible) and their families was overwhelmingly positive, partly due to (a) the system's ease of use, (b) its ability to reduce the number of admissions/tests required and (c) the facility for rapid measurement of ICP that permitted on-the-spot reassurance of concerns. Additionally, the ability to monitor ICP at home and/or whilst ambulant, has provided measurements that were hitherto inaccessible to our team, facilitating all the potential benefits that analysis of such information would provide. Indeed, we have seen the resultant management in each case has been completely altered by the availability of this data, reaffirming that the importance of being able to obtain it should not be underestimated. The combination of both this and the ability to markedly improve patient experience, along with generating significant cost-savings, lead the authors to suggest that the implantation of this system should be strongly considered in selected individuals.

Twenty-Year Review of a Single Surgeon's Experience Using a Unique Surgical Technique to Correct Lambdoidal Synostosis.

BACKGROUND: Numerous techniques for the surgical management of lambdoidal synostosis have been previously described; however, no best practice technique currently exists. Surgical procedures range from complete posterior calvarial reconstruction to distraction osteogenesis techniques. Our primary purpose is to describe a novel approach to correct unilateral or bilateral lambdoidal synostosis. METHODS: A retrospective review was performed on a single surgeon's experience with craniosynostosis (1994-2014). Specifically, craniosynostosis cases involving the lambdoidal suture, which were repaired using a novel 'tongue and groove' technique, were identified. RESULTS: A total of 664 craniosynostosis cases were retrieved, with 21 primarily involving the lambdoidal suture (3.2%). Of these, 18 were unilateral and 3 were bilateral lambdoidal synostosis. Male-to-female ratio was 3:1. Average age of first encounter with a craniofacial physician was 33 weeks (8 months). Average age at time of surgery was 43 weeks (10.75 months). Complications of this technique included 1 patient who experienced refusion of his lambdoidal suture and fusion of his sagittal suture, and 4 who returned for bone graft coverage of full-thickness calvarial defects owing to a lack of complete reossification. CONCLUSION: The "tongue and groove" technique represents a novel method for the management of lambdoidal synostosis with good esthetic outcomes, allowing immediate cranial stabilization with increased skull volume. This technique, used by the senior author for >20 years, provides a reproducible and reliable method of correcting lambdoidal synostosis.

Antioxidant and chelating capacity of Maillard reaction products in amino acid-sugar model systems: applications for food processing.

BACKGROUND: Maillard reaction products (MRP) have gained increasing interest owing to their both positive and negative effects on human health. Aqueous amino acid-sugar model systems were studied in order to evaluate the antioxidant and chelating activity of MRP under conditions similar to those of food processing. Amino acids (cysteine, glycine, isoleucine and lysine) combined with different sugars (fructose or glucose) were heated to 100 and 130 °C for 30, 60 and 90 min. Antioxidant capacity was evaluated via ABTS and DPPH free radical scavenging assays, in addition to Fe2+ and Cu2+ ion chelating capacity. RESULTS: In the ABTS assay, the cysteine-fructose model system presented the highest antioxidant activity at 7.05 µmol mL-1 (130 °C, 60 min), expressed in Trolox equivalents. In the DPPH assay, the cysteine-glucose system presented the highest antioxidant activity at 3.79 µmol mL-1 (100 °C, 90 min). The maximum rate of chelation of Fe2+ and Cu2+ was 96.31 and 59.44% respectively in the lysine-fructose and cysteine-glucose systems (100 °C, 30 min). CONCLUSION: The model systems presented antioxidant and chelating activity under the analyzed temperatures and heating times, which are similar to the processing conditions of some foods. © 2017 Society of Chemical Industry.

Cosmetic Liposuction: Preoperative Risk Factors, Major Complication Rates, and Safety of Combined Procedures.

BACKGROUND: Liposuction is among the most commonly performed aesthetic procedures, and is being performed increasingly as an adjunct to other procedures. OBJECTIVES: To report the incidence and risk factors of significant complications after liposuction, and to determine whether adding liposuction to other cosmetic surgical procedures impacts the complication risk. METHODS: A prospective cohort of patients who underwent liposuction between 2008 and 2013 was identified from the CosmetAssure database. Primary outcome was occurrence of major complications requiring emergency room visit, hospital admission, or reoperation within 30 days of the operation. Univariate and multivariate analysis evaluated risk factors including age, gender, body mass index (BMI), smoking, diabetes, type of surgical facility, and combined procedures. RESULTS: Of the 31,010 liposuction procedures, only 11,490 (37.1%) were performed as a solitary procedure. Liposuction alone had a major complication rate of 0.7% with hematoma (0.15%), pulmonary complications (0.1%), infection (0.1%), and confirmed venous thromboembolism (VTE) (0.06%) being the most common. Independent predictors of major complications included combined procedures (Relative Risk (RR) 4.81), age (RR 1.01), BMI (RR 1.05), and procedures performed in hospitals (RR 1.36). When examining specifically other aesthetic procedures performed alone or with liposuction, combined procedures had a higher risk of confirmed VTE (RR 5.65), pulmonary complications (RR 2.72), and infection (RR 2.41), but paradoxically lower hematoma risk (RR 0.77) than solitary procedures. CONCLUSIONS: Liposuction performed alone is a safe procedure with a low risk of major complications. Combined procedures, especially on obese or older individuals, can significantly increase complication rates. The impact of liposuction on the risk of hematoma in combined procedures needs further investigation.

Prolonged persistence of a novel replication-defective HIV-1 variant in plasma of a patient on suppressive therapy.

BACKGROUND: Cell-free residual HIV-1 virions (RVs) persist in plasma below 20-50 vRNA copies/ml in most patients on suppressive antiretroviral therapy (ART). How RVs are produced in the body during therapy is not fully clear. In this study, we have attempted to characterize these viruses of an ART-treated patient in vitro in order to gain insights into the mechanism of their production in vivo. METHODS: We have reconstructed almost the entire genomes of RVs as DNA forms using the patient's residual plasma vRNA by an overlapping RT-nested PCR method, and then sequence-analyzed the cloned genomes and tested them for their biological activities in vitro. RESULTS: We found that the reconstructed molecular clones of RVs lacked antiretroviral drug-resistant mutations, as well as G-to-A hypermutations. The vDNA clones, when transfected into TZM-bl cells, released HIV-p24 into the culture media at extremely low levels. This low-level virus production was found to be due to the presence of a unique mutation (GU-to-GC) in the conserved 5'-major splice donor (MSD) motif of the corresponding vRNAs. We found that the incorporation of this point mutation by itself could cause defects in the replication of a standard HIV strain (JRCSF) in vitro. However, this novel viral variant was intermittently detected at 5 of 7 time-points in the patient's plasma over a period of 39 months during therapy. CONCLUSIONS: This is the first identification of a natural point mutation (GU-to-GC) in the conserved 5'-MSD motif of HIV genomic RNA. The intermittent but prolonged detection of this replication-defective HIV variant in the patient's plasma among other viral populations strongly suggests that this variant is released from highly stable productively infected cells present in vivo during therapy. The potential implication of this observation is that the elimination of such productively infected cells that contribute to residual viremia during suppressive therapy could be an important first step towards achieving a cure for HIV.

Surgery for epilepsy.

BACKGROUND: Focal epilepsies are caused by a malfunction of nerve cells localised in one part of one cerebral hemisphere. In studies, estimates of the number of individuals with focal epilepsy who do not become seizure-free despite optimal drug therapy vary according to the age of the participants and which focal epilepsies are included, but have been reported as at least 20% and in some studies up to 70%. If the epileptogenic zone can be located surgical resection offers the chance of a cure with a corresponding increase in quality of life. OBJECTIVES: The primary objective is to assess the overall outcome of epilepsy surgery according to evidence from randomised controlled trials.The secondary objectives are to assess the overall outcome of epilepsy surgery according to non-randomised evidence and to identify the factors that correlate to remission of seizures postoperatively. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (June 2013), the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 6), MEDLINE (Ovid) (2001 to 4 July 2013), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for relevant trials up to 4 July 2013. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs), cohort studies or case series, with either a prospective and/or retrospective design, including at least 30 participants, a well-defined population (age, sex, seizure type/frequency, duration of epilepsy, aetiology, magnetic resonance imaging (MRI) diagnosis, surgical findings), an MRI performed in at least 90% of cases and an expected duration of follow-up of at least one year, and reporting an outcome relating to postoperative seizure control. DATA COLLECTION AND ANALYSIS: Three groups of two review authors independently screened all references for eligibility, assessed study quality and risk of bias, and extracted data. Outcomes were proportion of participants achieving a good outcome according to the presence or absence of each prognostic factor of interest. We intended to combine data with risk ratios (RR) and 95% confidence intervals. MAIN RESULTS: We identified 177 studies (16,253 participants) investigating the outcome of surgery for epilepsy. Four studies were RCTs (including one that randomised participants to surgery or medical treatment). The risk of bias in the RCTs was unclear or high, limiting our confidence in the evidence that addressed the primary review objective. Most of the remaining 173 non-randomised studies had a retrospective design; they were of variable size, were conducted in a range of countries, recruited a wide demographic range of participants, used a wide range of surgical techniques and used different scales used to measure outcomes. We performed quality assessment using the Effective Public Health Practice Project (EPHPP) tool and determined that most studies provided moderate or weak evidence. For 29 studies reporting multivariate analyses we used the Quality in Prognostic Studies (QUIPS) tool and determined that very few studies were at low risk of bias across the domains.In terms of freedom from seizures, one RCT found surgery to be superior to medical treatment, two RCTs found no statistically significant difference between anterior temporal lobectomy (ATL) with or without corpus callosotomy or between 2.5 cm or 3.5 cm ATL resection, and one RCT found total hippocampectomy to be superior to partial hippocampectomy. We judged the evidence from the four RCTs to be of moderate to very low quality due to the lack of information reported about the randomised trial design and the restricted study populations.Of the 16,253 participants included in this review, 10,518 (65%) achieved a good outcome from surgery; this ranged across studies from 13.5% to 92.5%. Overall, we found the quality of data in relation to the recording of adverse events to be very poor.In total, 118 studies examined between one and eight prognostic factors in univariate analysis. We found the following prognostic factors to be associated with a better post-surgical seizure outcome: an abnormal pre-operative MRI, no use of intracranial monitoring, complete surgical resection, presence of mesial temporal sclerosis, concordance of pre-operative MRI and electroencephalography (EEG), history of febrile seizures, absence of focal cortical dysplasia/malformation of cortical development, presence of tumour, right-sided resection and presence of unilateral interictal spikes. We found no evidence that history of head injury, presence of encephalomalacia, presence of vascular malformation or presence of postoperative discharges were prognostic factors of outcome. We observed variability between studies for many of our analyses, likely due to the small study sizes with unbalanced group sizes, variation in the definition of seizure outcome, definition of the prognostic factor and the influence of the site of surgery, all of which we observed to be related to postoperative seizure outcome. Twenty-nine studies reported multivariable models of prognostic factors and the direction of association of factors with outcome was generally the same as found in the univariate analyses. However, due to the different multivariable analysis approaches and selective reporting of results, meaningful comparison of multivariate analysis with univariate meta-analysis is difficult. AUTHORS' CONCLUSIONS: The study design issues and limited information presented in the included studies mean that our results provide limited evidence to aid patient selection for surgery and prediction of likely surgical outcome. Future research should be of high quality, have a prospective design, be appropriately powered and focus on specific issues related to diagnostic tools, the site-specific surgical approach and other issues such as the extent of resection. Prognostic factors related to the outcome of surgery should be investigated via multivariable statistical regression modelling, where variables are selected for modelling according to clinical relevance and all numerical results of the prognostic models are fully reported. Protocols should include pre- and postoperative measures of speech and language function, cognition and social functioning along with a mental state assessment. Journal editors should not accept papers where adverse events from a medical intervention are not recorded. Improvements in the development of cancer care over the past three to four decades have been achieved by answering well-defined questions through the conduct of focused RCTs in a step-wise fashion. The same approach to surgery for epilepsy is required.

Association between high serum estradiol levels and delirium among hospitalized elderly women.

BACKGROUND: Delirium is a common and serious disorder among hospitalized elderly individuals. We investigated the association between serum estradiol levels and incident delirium. METHODS: Longitudinal study of 141 women ≥ 70 years old admitted to a tertiary care hospital in Mexico City. All participants underwent a comprehensive geriatric assessment. Blood samples for cortisol and estradiol determination were obtained at hospital admission. Incident delirium was investigated until participants were discharged. Multivariate models were run to test the independent association between estradiol levels and incident delirium. RESULTS: Twenty-three (16.3%) participants developed delirium. Estradiol levels were higher among women with incident delirium compared with non-affected women. Multivariate logistic regression analysis showed that serum estradiol levels were associated with incident delirium even after adjusting for multiple confounding covariates, including cortisol levels (OR: 1.93; 95% CI: 1.28-2.92). CONCLUSIONS: Elderly women with high serum estradiol levels at hospital admission had an increased risk for incident delirium. Serum estradiol may be a biomarker for increased risk of delirium.