HIV infection among men who have sex with men in Israel: a 35-year epidemiological and clinical overview, 1981-2015.

BACKGROUND: This study is the first to describe major epidemiological trends and clinical characteristics among Israeli men who have sex with men (MSM), who are at a higher risk for HIV infection. METHODS: This retrospective study includes all individuals reported to the Israeli Ministry of Health with HIV and self-identified as MSM between 1981 and 2015. The incidence rates of HIV infection and AIDS-defining diseases were analyzed and Kaplan-Meier survival estimates were calculated from time of HIV infection notification to AIDS diagnosis and death across three consecutive periods representing antiretroviral treatment availability. RESULTS: The trend of increase in HIV incidence is similar to Western Europe, although Israeli rates are lower. Of 2052 HIV/AIDS Israeli MSM diagnosed during the follow-up, 296 (14.6%) developed AIDS. MSM constitute 28.4% of all HIV/AIDS cases and 41.5% of cases among men. Average times from HIV-notification until AIDS diagnosis were 15.5 [14.0-16.9], 16.0 [15.5-16.4], and 6.7 [6.7-6.8] years, within 1981-1996, 1997-2007, and 2008-2015, respectively. The HIV-incidence rate among Israeli MSM slightly declined from 2012, after peaking in 2011 at 6.2 per 100,000. CONCLUSIONS: The recent reduction in HIV-incidence and in AIDS diagnoses among Israeli MSM is encouraging. Nevertheless, the disproportionate incidence of HIV among MSM requires sustained efforts to abate further infections.

The relation between gain in cognition during rehabilitation on functional outcome among hip fracture adult patients with and without pre- hip fracture dementia.

The purpose of the present study was focused on the relationship between change in cognition and the functional outcome during rehabilitation in demented and non-demented adult hip fracture patients. We studied seventy consecutive adult patients with hip fracture admitted to our rehabilitation wards. Functional outcome was assessed by the Functional Independence Measure (FIM). The gain in cognition during the rehabilitation process was measured by the difference in Mini Mental State Examination scores at admission and discharge. Data was analyzed by t-test, chi square-test and linear regression. Patients without dementia presented and discharged from the rehabilitation ward with statistically significant higher total, motor, and gain functional independence measure scores compared to patients with dementia. In a multiple regression analyses, gain in Mini Mental State scores examination were not independently associated with higher total and motor functional independence measure scores at discharge (beta = 0.086, p = 0.194; beta = 0.077, p = 0.309, respectively). Our findings suggest that there is no association between functional outcome and cognitive gain at the end of the rehabilitation process among adult hip fracture patients with and without dementia. However hip fracture adult patients with dementia should not be deprived of a post-acute rehabilitation.

Survey results of currently used techniques and materials by dentists for fabrication of complete removable dental prostheses.

The present study was based on the screening of procedures and materials used by dentists in constructing complete removable dental prostheses, considering their professional background and years of experience. Questions arose regarding differences and similarities within the local dental society, of which approximately 75% were trained in Europeans countries with differences in academic background, and compared to international dentistry. A questionnaire web site was used in order to anonymously collect answers to the survey by general practicing and specialist dentists. The survey contained 28 multiple choice questions that were based on 5 parameters: years of experience, location of dental studies, specialization, location and field of specialization. One hundred one survey sheets were collected. The results show statistical significance (p less than 0.05) for the following comparisons: practicing time had an impact on practitioner-technician interaction, while the level of qualification had an effect on articulator and face-bow usage. Location of dental studies, specialization and residency had impact on final impression materials, teeth set-up as well as tooth shape and color selection. The differences found between dentists’ working techniques set the ground for future research that should focus on rating the success of the different methods towards a goal of creating recommendations for an ideal set of working techniques.

Interoperable atlases of the human brain.

The last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different aspects of the human brain including micro- and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topographically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and representation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored.

[Impressions for implant supported prostheses].

A crucial aspect for successful outcome of implant supported restoration is it's accurate fit. The implant and the prosthetic component have precise machine fit, thus small discrepancies can lead to stress applied to the implants when connecting the restoration. The accuracy of the master cast is of great significance and depends on both clinical and laboratory factors. The purpose of this article is to discuss the various materials and methods available for impressions and the effect of implants' location, number and angulations on the accuracy of the impressions.

[Current status of implant-abutment--part 1: abutments for cemented versus screw retained restorations].

Fixed implant supported single crowns and fixed dental prostheses (FDPs) have become an accepted treatment option for replacing and restoring missing teeth. Recent systematic reviews summarized excellent 5- and 10-year survival rates for both reconstruction types. In screw-retained restorations, the fastening screw provides a solid joint between the restoration and the implant abutment or between the restoration and the implant itself. With cement-retained prostheses, this restorative screw is eliminated for many reasons: esthetics, occlusal stability, and fabrication of passively fitting restorations. The purpose of this article is to review the variety of implant-abutments available for fabrication of fixed implant-supported restoration and compare between the various abutment forms (screw vs. cement retained).

[The influence of dental implant surface on osseointegration: review].

Dental implant therapy is a prevalent and successful treatment, based on research and clinical experience. Ossointegration is the main factor that responsible for success or failure, initially of the implant, and in some cases followed with the whole treatment failure. The osseointegration process is influenced by several factors, among them the surface texture. Dental implants are available with different surface modifications that have been developed for enhancing clinical performances. This paper reviews the main treatments used for changing dental titanium implant surfaces, and compare the clinical performance of different types of implants. Based on existent literature, modified implant surface improves significantly the ability to achive optimise bone-implant contact and improve osseointegration. This review did not find any significant major differences between the surface modifications in use this days in terms of survival and success of specific implant. There are several methods that are no longer in use, due to poor clinical performance in the past.

The Human Connectome Project: a data acquisition perspective.

The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize brain connectivity and function and their variability in healthy adults. This review summarizes the data acquisition plans being implemented by a consortium of HCP investigators who will study a population of 1200 subjects (twins and their non-twin siblings) using multiple imaging modalities along with extensive behavioral and genetic data. The imaging modalities will include diffusion imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography and electroencephalography (MEG/EEG). Given the importance of obtaining the best possible data quality, we discuss the efforts underway during the first two years of the grant (Phase I) to refine and optimize many aspects of HCP data acquisition, including a new 7T scanner, a customized 3T scanner, and improved MR pulse sequences.

Dysregulation of kisspeptin and neurogenesis at adolescence link inborn immune deficits to the late onset of abnormal sensorimotor gating in congenital psychological disorders.

Neuropsychological syndromes including schizophrenia often do not manifest until late adolescence or early adulthood. Studies attributing a role in brain maintenance to the immune system led us to propose that malfunction of immune-dependent regulation of brain functions at adolescence underlies the late onset of such diseases/syndromes. One such function is sensorimotor gating, the ability to segregate a continuous stream of sensory and cognitive information, and to selectively allocate attention to a significant event by silencing the background (measured by prepulse inhibition; PPI). This activity is impaired in schizophrenia, as well as in several other neuropsychological diseases. Using a model of prenatal immune activation (maternal polyriboinosinic-polyribocytidylic acid (poly I:C) injection), often used as a model for schizophrenia, and in which abnormal PPI has a delayed appearance, we demonstrated a form of immune deficit in the adult offspring. Similar abnormal PPI with a delayed appearance was found in congenitally immune-deficient mice (severe combined immune deficient, SCID), and could be reversed by immune reconstitution. This functional deficit correlated with impairment of both hippocampal neurogenesis and expression of the gene encoding kisspeptin (Kiss1) that manifested at adulthood. Moreover, exogenous administration of a kisspeptin-derived peptide partially reversed the gating deficits in the SCID mice. Our results suggest that a form of congenital immune deficiency may be a key factor that determines manifestation of developmental neuropsychological disorders with onset only at early adulthood.

Age-dependent spatial memory loss can be partially restored by immune activation.

Aging is often associated with a decline in hippocampus-dependent spatial memory. Here, we show that functional cell-mediated immunity is required for the maintenance of hippocampus-dependent spatial memory. Sudden imposition of immune compromise in young mice caused spatial memory impairment, whereas immune reconstitution reversed memory deficit in immune-deficient mice. Analysis of hippocampal gene expression suggested that immune-dependent spatial memory performance was associated with the expression of insulin-like growth factor (Igf1) and of genes encoding proteins related to presynaptic activity (Syt10, Cplx2). We further showed that memory loss in aged mice could be attributed to age-related attenuation of the immune response and could be reversed by immune system activation. Homeostatic-driven proliferation of lymphocytes, which expands the existing T cell repertoire, restored spatial memory deficits in aged mice. Thus, our results identify a novel function of the immune system in the maintenance of spatial memory and suggest an original approach for arresting or reversing age-associated memory loss.

Endovascular mechanical thrombectomy of an occluded superior division branch of the left MCA for acute cardioembolic stroke.

Cardiac embolism accounts for a large proportion of ischemic stroke. Revascularization using systemic or intra-arterial thrombolysis is associated with increasing risks of cerebral hemorrhage as time passes from stroke onset. We report successful mechanical thrombectomy from a distal branch of the middle cerebral artery (MCA) using a novel technique. A 72-year old man suffered an acute ischemic stroke from an echocardiographically proven ventricular thrombus due to a recent myocardial infarction. Intraarterial administration of 4 mg rt-PA initiated at 5.7 hours post-ictus failed to recanalize an occluded superior division branch of the left MCA. At 6 hours, symptomatic embolic occlusion persisted. Mechanical extraction of the clot using an Attracter-18 device (Target Therapeutics, Freemont, CA) resulted in immediate recanalization of the MCA branch. Attracter-18 for acute occlusion of MCA branches may be considered in selected patients who fail conventional thrombolysis or are nearing closure of the therapeutic window for use of thrombolytic agents.

Arterial blood supply to the auditory cortex of the chinchilla.

Utilizing optical imaging we identified and named the arteries that supply the primary auditory cortex in the chinchilla (Chinchilla laniger). The primary auditory cortex is located 2-3 mm caudal to the medial cerebral artery and is supplied by it. Using corrosion casts and scanning electron microscopy we visualized the capillary networks in the auditory cortex and found regional variations in the densities of the capillary bed. We hypothesize that the uneven capillary densities observed in the auditory cortex correspond to neurologically more active areas.

Gene transfer of low levels of beta-glucuronidase corrects hepatic lysosomal storage in a large animal model of mucopolysaccharidosis VII.

Gene therapy has been at least partially effective in several mouse disease models, but treatment of large mammals has been more difficult to achieve. One major limitation is that only low levels of expression of the corrective gene are often maintained in vivo. In a mouse model of the lysosomal storage disease mucopolysaccharidosis (MPS) type VII (Sly disease) with a null mutation in beta-glucuronidase, gene transfer experiments have shown that only 1-2% of normal beta-glucuronidase can correct the storage in some major organs. In contrast, MPS VII dogs, cats, and humans that have residual beta-glucuronidase activity levels in this range are affected. Thus, higher levels of transferred gene expression may be needed to achieve a therapeutic effect in large animals and humans. We tested this by examining liver pathology in MPS VII dogs after intraperitoneal transplantation of neo-organs containing retrovirus vector-corrected autologous fibroblasts that expressed low levels of beta-glucuronidase. The enzyme secreted from the neo-organs was taken up by the liver and significantly reduced the substrate content compared with untreated dogs. This suggests that small amounts of normal enzyme, when delivered to target tissues, may be therapeutically effective in human MPS VII patients.

Tonotopic mapping in auditory cortex of the adult chinchilla with amikacin-induced cochlear lesions.

We have found a reorganization of tonotopic maps (based on neuron response thresholds) in primary auditory cortex of the adult chinchilla after amikacin-induced basal cochlear lesions. We find an over-representation of a frequency that corresponds to the border area of the cochlear lesion. The reorganization observed is similar in extent to that previously seen in a developmental model. The properties of neurons within the over-represented area were investigated in order to determine whether their responses originated from a common input (an indication of true plasticity) or represented only the result of truncating the activity of the sensory epithelium ("pseudo-plasticity"). Some aspects of our data fit with a true plasticity model and indicate the potential for the deafferented cortex of the mature cortex to regain connections with the surviving sensory epithelium.

Three distinct auditory areas of cortex (AI, AII, and AAF) defined by optical imaging of intrinsic signals.

Using pure-tone sound stimulation, three separate auditory areas are revealed by optical imaging of intrinsic signals in the temporal cortex of the chinchilla (Chinchilla laniger). These areas correlate with primary auditory cortex (AI) and two secondary areas, AII and the anterior auditory field (AAF). We have distinguished AI on the basis of concurrent single-unit electrophysiological recording; neurons within the AI intrinsic signal region have short (<15 ms) onset-response latencies compared with neurons recorded in AII and the AAF. Within AI, AII, and AAF we have been able to define cochleotopic or tonotopic organization from the differences in intrinsic signal areas evoked by pure tones at octave-spaced frequencies from 500 Hz to 16 kHz. The maps in AI and AII are arranged orthogonal to each other.

Local haemodynamic changes associated with neural activity in auditory cortex.

We used an optical technique to study haemodynamic changes associated with acoustically driven activity in auditory cortex of the chinchilla. Such changes are first detectable c. 0.5 s after stimulation, peak at 2-3 s, and decay within a further 3-6 s. This intrinsic signal imaging reveals activity in separate cortical areas, including primary auditory cortex (AI), secondary auditory cortex (AII) and an anterior auditory field (AAF). We have measured the timing of haemodynamics associated with each area, and find that AI has a different time course from AII and AAF; its haemodynamic change recovers more rapidly. We also show that within AI and AII, place specific activity related to acoustic stimulus frequency can be resolved by this optical imaging method. Our results show the close association between blood flow change and the local metabolic demands of neural activity. The data provide information about the potential of other functional imaging methods (e.g. PET, fMRI) which rely on activity related haemodynamic events.

Comparison of distortion-product and transient evoked otoacoustic emissions with ABR threshold shift in chinchillas with ototoxic damage.

In this study we compare distortion product otoacoustic emissions (DPOAEs), transient evoked otoacoustic emissions (TEOAEs) and ABR threshold shifts in an animal model (chinchilla) of cochlear hearing loss. Subjects were treated with an aminoglycoside (amikacin) to produce basal cochlear lesions of various degree. DPOAE and TEOAE were measured throughout the treatment period and until hearing thresholds stabilized. ABR thresholds to tone pip stimuli were determined. Cytocochleograms of cochleas were prepared using scanning microscopy. DPOAEs (2f1-f2) were compared to fast Fourier transform (FFT)-analyzed TEOAEs components in the 1-, 2-, and 4-kHz frequency regions. Both types of emission were compared with corresponding ABR thresholds. There was no significant linear correlation between these different measures of cochlear function. Moreover, the amplitudes of DPOAEs reflected smaller regions of cochlear outer hair cell (OHC) damage better than TEOAEs. These results suggest that DPOAEs can be used to more accurately monitor hair cell function at specific hearing locations than TEOAEs.

Basal cochlear lesions result in increased amplitude of otoacoustic emissions.

We have measured the changes in transient otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) during and after ototoxic amikacin treatment in an animal (chinchilla) model. TEOAE and DPOAE were recorded from 6 adult chinchillas over a 6-week time course starting just before a 5-day or 7-day treatment period with amikacin sulphate (400 mg/kg/day, i.m.). After final recordings, cochlear morphology was assessed by scanning electron microscopy. Generally, both DPOAE and TEOAE amplitudes change during and after treatment in a systematic fashion. High-frequency components change first, followed by lower-frequency components. We note that there is often a long latency to the onset of changes in otoacoustic emissions (OAE), and that these changes can continue for weeks after treatment. Most importantly we report that when the basal region of the cochlea is damaged in the frequency region above the OAE recording bandwidth (0.6-6 kHz for TEOAE; 1-6.7 kHz for DPOAE), we often find an increase in OAE amplitudes. More specifically, we note that as a cochlear lesion progresses apically, there is often a transient increase in a frequency-specific OAE before it reduces or is lost. Our results suggest that the increase in OAE amplitudes precedes the expression of detectable cochlear pathology.

Phosphorylation of the human cytomegalovirus 86-kilodalton immediate-early protein IE2.

We have investigated the phosphorylation state of the human cytomegalovirus 86-kDa immediate-early (IE) protein IEP86 from transfected and infected cells. We show that multiple domains of IEP86 are phosphorylated by cellular kinases, both in vitro and in vivo. Our data suggest that serum-inducible kinases play a significant role in cell-mediated IE protein phosphorylation and that a member of the mitogen-activated protein (MAP) kinase (MAPK) family, extracellular regulated kinase 2 (ERK2), phosphorylates several domains of IEP86 in vitro. Alanine substitution mutagenesis was performed on specific serines or threonines (T27, S144, T233/S234, and T555) found in consensus MAP kinase motifs. Analysis of these mutations showed that T27 and T233/S234 are the major sites for serum-inducible kinases and are the major ERK2 sites in vitro. S144 appeared to be phosphorylated in a serum-independent manner in vitro. All of the mutations except T555 eliminated specific phosphorylation in vivo. In transient transfection analyses, IEP86 isoforms containing mutations in S144 and, especially, T233/S234 displayed increased transcriptional activation relative to the wild type, suggesting that phosphorylation at these sites in wild-type IEP86 may result in reduction of its transcriptional activation ability.

Optical imaging of intrinsic signals in chinchilla auditory cortex.

We have assessed sound frequency and intensity responses in primary auditory cortex of the (ketamine) anesthetized chinchilla using optical imaging of intrinsic signals. Temporal cortex was exposed via a 10-mm craniotomy and a windowed chamber was mounted. A 4-second period of gated tones (10 ms rise/fall; 50 ms plateau; 10/s) was presented to the contralateral ear at levels between 0 and 80 dB SPL. The cortical surface was illuminated with 540 nm light and video images captured in 0.5-second bins for 7.5 s (Imager 2001; Optical Imaging). Intrinsic signals were first apparent 0.5-1 s after stimulus onset, and were maximal after 3-4 s; they decayed over several seconds. The cortical area in which intrinsic activity was detected corresponded closely with electrophysiologically defined AI cortex. Intrinsic signals can reliably be detected to stimuli at 30-40 dB SPL, and in general, the area of intrinsic signal activity tends to expand with increasing stimulation level. Using stimulation levels of 80 dB SPL, we show that low-frequency stimuli (0.5-1 kHz) evoke intrinsic signals in anterior areas whilst posterior areas are activated by high-frequency stimuli (e.g. 16 kHz). Thus a low- to high-frequency tonotopic organization is seen along this axis.