Schizophrenia syndrome due to C9ORF72 mutation case report: a cautionary tale and role of hybrid brain imaging!

BACKGROUND: Frontal variant frontotemporal dementia is a common cause of presenile dementia. A hexanucleotide expansion on chromosome 9 has recently been recognized as the most common genetic mutation cause of this illness. This sub-type tends to present psychiatrically with psychosis being a common presenting symptom before the onset of cognitive changes or brain atrophy. A few case series have been published describing the prominence of early psychotic symptoms, and lack of clear brain atrophy on clinical brain imaging imposing a challenge in reaching early accurate diagnosis. In this report, we present a case whereby the diagnosis of Schizophrenia syndrome was made and the patient was treated for years with multiple interventions for that syndrome before reaching the accurate diagnosis of Frontal variant frontotemporal dementia due to hexanucleotide expansion on chromosome 9. This diagnosis was confirmed after genetic testing and findings on a hybrid Positron Emission Tomography/Magnetic Resonance Imaging scanning. A 60-year-old female diagnosed with schizophrenia at age 50 after presenting with delusions and hallucinations, which proved to be refractor to several lines of pharmacological and non-pharmacological interventions including electroconvulsive therapy. Patient had a history of post-partum psychosis in her 20s. She was referred to cognitive neurology due to progressive decline in function. While clinical structural brain imaging data were not adequate to support an alternative neurological diagnosis, careful inquiry elicited a history of psychotic illness followed by progressive decline in a sister. Genetic testing confirmed hexanucleotide expansion on chromosome 9 mutation. The patient was offered a state-of-the-art FD-Glucose Positron Emission Tomography/Magnetic Resonance Imaging scan available at our centre. While volumetric Magnetic Resonance Imaging scan did not show volume loss in frontotemporal areas, the hybrid scan showed regionally specific deficit in FD-Glucose Positron Emission Tomography affecting medial superior frontal, insula, inferior temporal, thalamus, and anterior cingulate cortex consistent with behavioral variant frontotemporal dementia. CONCLUSIONS: This case highlights the importance of considering Frontal variant frontotemporal dementia due to hexanucleotide expansion on chromosome 9 when facing relatively late-onset, refractory schizophrenia-like syndrome. Careful history from all available sources to elicit family history of similar presentation is very important. Genetic testing and functional brain imaging can aid in confirming the diagnosis and potentially streamlining the management of these cases.

Risk of dementia in bipolar disorder and the interplay of lithium: a systematic review and meta-analyses.

OBJECTIVES: To assess whether bipolar disorder (BD) increases the rate of dementia and whether lithium is related to a lower risk of dementia in BD. METHODS: A total of 10 studies (6859 BD; 487 966 controls) were included in the meta-analysis to test whether BD is a risk factor for dementia. In addition, five studies (6483 lithium; 43 496 non-lithium) were included in the meta-analysis about the potential protective effect of lithium in BD. RESULTS: BD increases the risk of dementia (odds ratio (OR): 2.96 [95% CI: 2.09-4.18], P < 0.001), and treatment with lithium decreases the risk of dementia in BD (OR: 0.51 [95% CI: 0.36-0.72], P < 0.0001). In addition, secondary findings from our systematic review showed that the risk of progression to dementia is higher in BD than in major depressive disorder (MDD). Moreover, the number of mood episodes predicted the development of dementia in BD. CONCLUSION: Individuals with BD are at higher risk of dementia than both the general population or those with MDD. Lithium appears to reduce the risk of developing dementia in BD.

Ambroxol as a novel disease-modifying treatment for Parkinson's disease dementia: protocol for a single-centre, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for ß-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The aims of this trial are to determine if Ambroxol is safe and well-tolerated by individuals with PDD and if Ambroxol affects cognitive, biochemical, and neuroimaging measures. METHODS: This is a phase II, single-centre, double-blind, randomized placebo-controlled trial involving 75 individuals with mild to moderate PDD. Participants will be randomized into Ambroxol high-dose (1050 mg/day), low-dose (525 mg/day), or placebo treatment arms. Assessments will be undertaken at baseline, 6-months, and 12-months follow up times. Primary outcome measures will be the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician's Global Impression of Change (CGIC). Secondary measures will include the Parkinson's disease Cognitive Rating Scale, Clinical Dementia Rating, Trail Making Test, Stroop Test, Unified Parkinson's disease Rating Scale, Purdue Pegboard, Timed Up and Go, and gait kinematics. Markers of neurodegeneration will include MRI and CSF measures. Pharmacokinetics and pharmacodynamics of Ambroxol will be examined through plasma levels during dose titration phase and evaluation of GCase activity in lymphocytes. DISCUSSION: If found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.

Defining the Tipping Point in Surgical Performance for Laparoscopic Donor Nephrectomy Among Transplant Surgery Fellows: A Risk-Adjusted Cumulative Summation Learning Curve Analysis.

The United Network for Organ Sharing recommends that fellowship-trained surgeons participate in 15 laparoscopic donor nephrectomy (LDN) procedures to be considered proficient. The American Society of Transplant Surgeons (ASTS) mandates 12 LDNs during an abdominal transplant surgery fellowship. We performed a retrospective intraoperative case analysis to create a risk-adjusted cumulative summation (RACUSUM) model to assess the learning curve of novice transplant surgery fellows (TSFs). Between January 2000 and December 2014, 30 novice TSFs participated in the organ procurement rotation of our ASTS-approved abdominal transplant surgery fellowship. Measures of surgical performance included intraoperative time, estimated blood loss, and incidence of intraoperative complications. The performance of senior TSFs was used to benchmark novice TSF performance. Scores were tabulated in a learning curve model, adjusting for case complexity and prior TSF case volume. Rates of adverse surgical events were significantly higher for novice TSFs than for senior TSFs. In univariable analysis, multiple renal arteries, high BMI, prior abdominal surgery, male donor, and nephrolithiasis were correlated with higher incidence of adverse surgical events. Based on the RACUSUM model, high intraoperative time is mitigated after 28 procedures, incidence of intraoperative complications tends to diminish after 24 procedures, and improvement in estimated blood loss did not remain consistent. TSFs exhibit a tipping point in LDN performance by 24-28 cases and proficiency by 35-38 cases.

HLA-A, -B, -C, -DR, and -DQ Matching in Pancreas Transplantation: Effect on Graft Rejection and Survival.

To enhance selection of appropriate deceased donors for pancreas transplants, we sought to determine whether HLA matching improved posttransplantation outcomes. In this single-center study of 1219 pancreas transplants, we correlated posttransplantation outcomes with HLA-A, -B, -C, -DR, and -DQ matches and mismatches. Rejection was linearly correlated with the number of mismatches. The individual number of HLA mismatches reached significance at four or more with a 2.3- to 2.9-fold increase in rejection. The effect was most predominant with HLA-B (1.8-fold with one mismatch and 2.0-fold with two mismatches) and -DR (1.9-fold with two mismatches) loci, whereas HLA-A, -C, and -DQ matches or mismatches did not independently predict acute rejection. The affect was strongest in solitary pancreas transplants, with little impact for simultaneous pancreas and kidney (SPK). In contrast, HLA matching did not affect graft or patient survival rates but was associated with a reduced risk of opportunistic infection. Avoidance of acute rejection saved an estimated $32 000 for solitary pancreas recipients and $52 000 for SPK recipients in hospital costs. Our data do not support the use of HLA matching for predicting pancreas graft survival but do support its significance for the reduction of acute rejection, particularly for solitary pancreas recipients.

Progressive supranuclear palsy in a family with TDP-43 pathology.

UNLABELLED: A member of a family with an autosomal dominant pattern of frontotemporal dementia (FTD) with a TDP-43 pathological substrate in other members and no mutations in FTD-associated genes developed behavioral variant FTD followed by Progressive Supranuclear Palsy. Autopsy revealed a pure tauopathy of PSP pattern. CONCLUSIONS: The findings raise the possibility of shared pathogenic pathways and a proximal genetic abnormality between PSP and FTLD-43.

A composite risk model for predicting technical failure in pancreas transplantation.

Technical failure (TF) continues to have a significant impact on the success of pancreas transplantation. We assessed risk factors for TF in 1115 pancreas transplants performed at a single center between 1998 and 2011. The overall TF rate was 10.2%. In a multivariable model, donor BMI ≥ 30 (HR 1.87, p = 0.005), donor Cr ≥ 2.5 (HR 3.16, p = 0.007), donor age >50 (HR 1.73, p = 0.082) and preservation time >20 h (HR 2.17, p < 0.001) were associated with TF. Bladder drainage of exocrine secretions was protective (HR 0.54, p = 0.002). We incorporated these factors in a Composite Risk Model. In this model the presence of one risk factor did not significantly increase risk of TF (HR 1.35, p = 0.346). Two risk factors in combination increased risk greater than threefold (HR 3.65, p < 0.001) and three risk factors increased risk greater than sevenfold (HR 7.66, p = <0.001). The analysis also identified many factors that were not predictive of TF, including previous transplants, immunosuppressive agent selection, and almost all recipient demographic parameters. While the model suggests that two or more risk factors predict TF, strategies to reduce preservation time may mitigate some of this risk.

Prospective randomized trial of maintenance immunosuppression with rapid discontinuation of prednisone in adult kidney transplantation.

Rapid discontinuation of prednisone (RDP) has minimized steroid-related complications following kidney transplant (KT). This trial compares long-term (10-year) outcomes with three different maintenance immunosuppressive protocols following RDP in adult KT. Recipients (n=440; 73% living donor) from March 2001 to April 2006 were randomized into one of three arms: cyclosporine (CSA) and mycophenolate mofetil (MMF) (CSA/MMF, n=151); high-level tacrolimus (TAC, 8-12 µg/L) and low-level sirolimus (SIR, 3-7 µg/L) (TACH/SIRL, n=149) or low-level TAC (3-7 µg/L) and high-level SIR (8-12 µg/L) (TACL/SIR(H) , n=140). Median follow-up was ∼7 years. There were no differences between arms in 10-year actuarial patient, graft and death-censored graft survival or in allograft function. There were no differences in the 10-year actuarial rates of biopsy-proven acute rejection (30%, 26% and 20% in CSA/MMF, TACH/SIRL and TACL/SIRH) and chronic rejection (38%, 35% and 31% in CSA/MMF, TACH/SIRL and TACL/SIRH). Rates of new-onset diabetes mellitus were higher with TACH/SIRL (p=0.04), and rates of anemia were higher with TACH/SIRL and TACL/SIRH (p=0.04). No differences were found in the overall rates of 16 other post-KT complications. These data indicate that RDP-based protocol yield acceptable 10-year outcomes, but side effects differ based on the maintenance regimen used and should be considered when optimizing immunosuppression following RDP.

Changes in motor activity level in individuals with frontotemporal dementia.

Changes in motor activity are common in individuals with Frontotemporal dementia (FTD). Yet, it remains unclear why some individuals become motorically hyperactive, while others hypoactive even in early stages of the disease. This study aimed to examine the relationship between motor activity level and (1) FTD clinical subtype, and (2) cortical thickness and subcortical volumes. Eighty-two charts were retrospectively reviewed from patients meeting consensus criteria for one of the three main clinical subtypes of FTD: probable bvFTD, semantic variant Primary Progressive Aphasia (PPA), or non-fluent variant PPA. Participants were assigned to one of three groups: (1) hyperactive, (2) hypoactive, or (3) no record of change. Hyperactivity was prevalent among bvFTD (58.5%) and semantic PPA (68.8%) subtypes while hypoactivity was less common in both subtypes (29.3% and 18.8%, respectively). The majority of patients with non-fluent PPA showed no record of change in motor activity (66.7%). The analysis of cortical thickness and subcortical volumes did not identify significant associations with motor activity levels. In conclusion, increased motor activity is highly prevalent among individuals with FTD, especially bvFTD and svPPA subtypes. These findings may inform prognosis and prediction of changes in motor activity, and allow planning for appropriate environmental and behavioural interventions. Future studies with prospective, standardized longitudinal collection of information regarding the type and level of change in motor activity, including wearable measures of actigraphy, may help to further delineate the onset and progression of abnormal motor behaviours and determine neuroanatomic associations in FTD.

Comparison of recipient outcomes following transplant from local versus imported pancreas donors.

The shortage of deceased donor organs for solid organ transplantation continues to be an ongoing dilemma. One approach to increase the number of pancreas transplants is to share organs between procurement regions. To assess for the effects of organ importation, we reviewed the outcomes of 1014 patients undergoing deceased donor pancreas transplant at a single center. We performed univariate and multivariate analyses of the association of donor, recipient and surgical characteristics with patient outcomes. Organ importation had no effect on graft or recipient survival for recipients of solitary pancreas transplants. Similarly, there was no effect on technical failure rate, graft survival or long-term patient survival for simultaneous kidney-pancreas (SPK) recipients. In contrast, there was a significant and independent increased risk of death in the first year in SPK recipients of imported organs. SPK recipients had longer hospitalizations and increased hospital costs. This increased medical complexity may make these patients more susceptible to short-term complications resulting from the longer preservation times of import transplants. These findings support the continued use of organ sharing to reduce transplant wait times but highlight the importance of strategies to reduce organ preservation times.

Impaired probabilistic reversal learning in youths with mood and anxiety disorders.

BACKGROUND: From an affective neuroscience perspective, our understanding of psychiatric illness may be advanced by neuropsychological test paradigms probing emotional processes. Reversal learning is one such process, whereby subjects must first acquire stimulus/reward and stimulus/punishment associations through trial and error and then reverse them. We sought to determine the specificity of previously demonstrated reversal learning impairments in youths with bipolar disorder (BD) by now comparing BD youths to those with severe mood dysregulation (SMD), major depressive disorder (MDD), anxiety (ANX), and healthy controls. METHOD: We administered the probabilistic response reversal (PRR) task to 165 pediatric participants aged 7-17 years with BD (n=35), SMD (n=35), ANX (n=42), MDD (n=18) and normal controls (NC; n=35). Our primary analysis compared PRR performance across all five groups matched for age, sex and IQ. RESULTS: Compared to typically developing controls, probabilistic reversal learning was impaired in BD youths, with a trend in those with MDD (p=0.07). CONCLUSIONS: Our results suggest that reversal learning deficits are present in youths with BD and possibly those with MDD. Further work is necessary to elucidate the specificity of neural mechanisms underlying such behavioral deficits.

Interactions through L-selectin between leukocytes and adherent leukocytes nucleate rolling adhesions on selectins and VCAM-1 in shear flow.

We demonstrate an additional step and a positive feedback loop in leukocyte accumulation on inflamed endothelium. Leukocytes in shear flow bind to adherent leukocytes through L-selectin/ligand interactions and subsequently bind downstream and roll on inflamed endothelium, purified E-selectin, P-selectin, L-selectin, VCAM-1, or peripheral node addressin. Thus adherent leukocytes nucleate formation of strings of rolling cells and synergistically enhance leukocyte accumulation. Neutrophils, monocytes, and activated T cell lines, but not peripheral blood T lymphocytes, tether to each other through L-selectin. L-selectin is not involved in direct binding to either E- or P-selectin and is not a major counterreceptor of endothelial selectins. Leukocyte-leukocyte tethers are more tolerant to high shear than direct tethers to endothelial selectins and, like other L-selectin-mediated interactions, require a shear threshold. Synergism between leukocyte-leukocyte and leukocyte-endothelial interactions introduces novel regulatory mechanisms in recruitment of leukocytes in inflammation.

The kinetics of L-selectin tethers and the mechanics of selectin-mediated rolling.

Two mechanisms have been proposed for regulating rolling velocities on selectins. These are (a) the intrinsic kinetics of bond dissociation, and (b) the reactive compliance, i.e., the susceptibility of the bond dissociation reaction to applied force. To determine which of these mechanisms explains the 7.5-11.5-fold faster rolling of leukocytes on L-selectin than on E- and P-selectins, we have compared the three selectins by examining the dissociation of transient tethers. We find that the intrinsic kinetics for tether bond dissociation are 7-10-fold more rapid for L-selectin than for E- and P-selectins, and are proportional to the rolling velocities through these selectins. The durations of pauses during rolling correspond to the duration of transient tethers on low density substrates. Moreover, applied force increases dissociation kinetics less for L-selectin than for E- and P-selectins, demonstrating that reactive compliance is not responsible for the faster rolling through L-selectin. Further measurements provide a biochemical and biophysical framework for understanding the molecular basis of rolling. Displacements of tethered cells during flow reversal, and measurements of the distance between successive pauses during rolling provide estimates of the length of a tether and the length of the adhesive contact zone, and suggest that rolling occurs with as few as two tethers per contact zone. Tether bond lifetime is an exponential function of the force on the bond, and the upper limit for the tether bond spring constant is of the same order of magnitude as the estimated elastic spring constant of the lectin-EGF unit. Shear uniquely enhances the rate of L-selectin transient tether formation, and conversion of tethers to rolling adhesions, providing further understanding of the shear threshold requirement for rolling through L-selectin.

Sialomucin CD34 is the major L-selectin ligand in human tonsil high endothelial venules.

Peripheral node addressin (PNAd) is a complex mixture of glycoproteins with L-selectin ligand activity that functions in lymphocyte homing. We have investigated the contribution of the sialomucin CD34 relative to other components of PNAd in lymphocyte tethering and rolling in in vitro laminar flow assays. PNAd was isolated with MECA-79 mAb-Sepharose from tonsillar stroma, and the CD34 component (PNAd,CD34+) and CD34-negative component (PNAd,CD34-) separated on CD34 mAb-Sepharose. Lymphocytes on the PNAd,CD34- fraction tether less efficiently, roll faster and are less resistant to shear detachment than on PNAd. The PNAd,CD34+ fraction constitutes about half the total functional activity. These studies show that CD34 is a major functional component of PNAd. Ligand activity in both the PNAd,CD34+ and PNAd,CD34- fractions is expressed on mucin-like domains, as shown with O-sialoglycoprotease. The CD34 component of PNAd has about four times higher tethering efficiency than total tonsillar CD34. CD34 from spleen shows no lymphocyte tethering. Although less efficient than the PNAd,CD34+ fraction from tonsil, CD34 from the KG1a hematopoietic cell line is functionally active as an L-selectin ligand despite lack of reactivity with MECA-79 mAb, which binds to a sulfation-dependent epitope. All four forms of CD34 are active in binding to E-selectin. KG1a CD34 but not spleen CD34 are active as L-selectin ligands, yet both lack MECA-79 reactivity and possess E-selectin ligand activity. This suggests that L-selectin ligands and E-selectin ligands differ in more respects than presence of the MECA-79 epitope.

The integrin VLA-4 supports tethering and rolling in flow on VCAM-1.

Selectins have previously been shown to tether a flowing leukocyte to a vessel wall and mediate rolling. Here, we report that an intergrin, VLA-4, can also support tethering and rolling. Blood T lymphocytes and alpha 4 integrin-transfected cells can tether in shear flow, and then roll, through binding of the intergrin VLA-4 to purified VCAM-1 on the wall of a flow chamber. VLA-4 transfectants showed similar tethering and rolling on TNF-stimulated endothelium. Tethering efficiency, rolling velocity, and resistance to detachment are related to VCAM-1 density. Tethering and rolling did not occur on ICAM-1, fibronectin, or fibronectin fragments, and tethering did not require integrin activation or the presence of an alpha 4 cytoplasmic domain. Arrest of rolling cells on VCAM-1 occurred spontaneously, and/or was triggered by integrin activating agents Mn2+, phorbol ester, and mAb TS2/16. These agents, and the alpha 4 cytoplasmic domain, promoted increased resistance to detachment. Together the results show that VLA-4 is a versatile integrin that can mediate tethering, rolling, and firm arrest on VCAM-1.

The role of 5-HTTLPR in choosing the lesser of two evils, the better of two goods: examining the impact of 5-HTTLPR genotype and tryptophan depletion in object choice.

RATIONALE: The serotonin (5-HT) system is considered important for decision-making. However, its role in reward- and punishment-based processing has not yet been clearly determined. OBJECTIVES: The present study examines the effect of 5-HTTLPR genotype and tryptophan depletion on reward- and punishment-related processing, using a task that considers decision-making in situations of subtlety of choice. Thus, it considers that response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or crème caramel cheesecake from a menu) or undesirable. It also considers that response choice is easier when the reinforcements associated with the options are far apart, rather than close, in value. MATERIALS AND METHODS: Healthy volunteers underwent acute tryptophan depletion (ATD) or control procedures and genotyping of the 5-HTTLPR for long and short allele variants. We then examined the effects and interactions of ATD and the serotonin promoter polymorphism genotype on two aspects of decision-making: (a) decision form, choosing between two objects to gain the greater reward or lesser punishment and (b) between-object reinforcement distance, the difference in reinforcements associated with two options. RESULTS: ATD and LL homozygosity had comparable interactions with decision form and between-object reinforcement distance. Specifically, both modulated the effect of between-object reinforcement distance when deciding between objects both associated with punishment. Moreover, ATD and genotype interacted with ATD disproportionately affecting the performance of the LL homozygous group. CONCLUSIONS: These results suggest that serotonin is particularly associated with punishment, rather than reward-related processing, and that individual sensitivity to punishment-related information and tryptophan depletion varies with genotype.

Eosinophil recruitment to the lung in a murine model of allergic inflammation. The role of T cells, chemokines, and adhesion receptors.

Eosinophil accumulation is a distinctive feature of lung allergic inflammation. Here, we have used a mouse model of OVA (ovalbumin)-induced pulmonary eosinophilia to study the cellular and molecular mechanisms for this selective recruitment of eosinophils to the airways. In this model there was an early accumulation of infiltrating monocytes/macrophages in the lung during the OVA treatment, whereas the increase in infiltrating T-lymphocytes paralleled the accumulation of eosinophils. The kinetics of accumulation of these three leukocyte subtypes correlated with the levels of mRNA expression of the chemokines monocyte chemotactic peptide-1/JE, eotaxin, and RANTES (regulated upon activation in normal T cells expressed and secreted), suggesting their involvement in the recruitment of these leukocytes. Furthermore, blockade of eotaxin with specific antibodies in vivo reduced the accumulation of eosinophils in the lung in response to OVA by half. Mature CD4+ T-lymphocytes were absolutely required for OVA-induced eosinophil accumulation since lung eosinophilia was prevented in CD4+-deficient mice. However, these cells were neither the main producers of the major eosinophilic chemokines eotaxin, RANTES, or MIP-1alpha, nor did they regulate the expression of these chemokines. Rather, the presence of CD4+ T cells was necessary for enhancement of VCAM-1 (vascular cell adhesion molecule-1) expression in the lung during allergic inflammation induced by the OVA treatment. In support of this, mice genetically deficient for VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmonary eosinophilia. Selective eosinophilic recruitment during lung allergic inflammation results from a sequential accumulation of certain leukocyte types, particularly T cells, and relies on the presence of both eosinophilic chemoattractants and adhesion receptors.

Biological aspects of bird colouration and avian colour vision including ultraviolet range.

Many diurnal birds possess a set of four spectrally different types of cone photoreceptor. The spectral range of vision is extended into the UV by a UV receptor. We have investigated the spectral properties of plumage colours including the UV by reflection spectroscopy. Some basic general principles of colour vision indicate that plumage colours are tuned to avian colour vision.

A 5-year study of the transmalar subperiosteal midface lift with minimal skin and superficial musculoaponeurotic system dissection: a durable, natural-appearing lift with less surgery and recovery time.

The transmalar subperiosteal midface lift is a simple, direct-approach procedure to be performed with a meloplasty. The entry into the midface is at the site of maximum suture tension, which allows for more elevation. The skin is elevated enough to expose the entry site, which is on the zygoma just cephalad to the origins of the zygomaticus muscles. Through a small hole at that site, a periosteal elevator is used for the midface dissection. This is a blind dissection, and the technique is described. The advantages of the technique are that there is (1) no lower-lid incision or risk of an ectropion, (2) a resultant tightening and elevation of the lower lid, (3) more elevation and durability because the zygomaticus muscle origins are elevated with the periosteum and are sutured to the very substantial deep temporal fascia, (4) a simple and fast procedure, and (5) no telltale sign of a face lift. Both the superficial musculoaponeurotic system (SMAS) and the skin are substantially elevated with the transmalar subperiosteal midface lift to the extent that they should be only minimally dissected. In the author's opinion, the extended dissection of the skin and/or the SMAS does not increase the amount of tissue lift and probably reduces it in most cases, considering that the goal is a natural look and not one that appears pulled or stretched. The skin is elevated only for exposure, and the SMAS is elevated only enough to create a preauricular SMAS-platysma flap to tighten the neck. With two fewer layers of dissection, there is significantly less postoperative swelling and recovery time. The article presents the technique, the results on 272 patients over a period of 5 years, and a discussion. No patients described have had secondary procedures such as lasers, so the transmalar subperiosteal midface lift can be evaluated on its own merit.

[Relation between coronary disease risk factors and mortality among men aged 40-59 years in the city of Frunze (5-year follow-up)]. / Vzaimosviaz' dinamiki faktorov riska ishemicheskoi bolezni serdtsa so smertnost'iu sredi muzhchin 40-59 let g. Frunze (za 5-letnii period).

The paper presents the dynamics of risk factors which was traced during prophylactic medical examinations and its relation to death rates among 40-59-year-old males from Frunze over 5 years. Prophylactic measures were found to lead to a positive dynamics of risk factors such as smoking, low physical activity, hypercholesterolemia, arterial hypertension in groups of active prevention. There was a decrease in death rates due to cardiovascular diseases, including myocardial infarction, stroke, among individuals with arterial hypertension, obesity, and low activity in the same group.