Lack of nAChR Activity Depresses Cochlear Maturation and Up-Regulates GABA System Components: Temporal Profiling of Gene Expression in α9 Null Mice

It has previously been shown that deletion of chrna9, the gene encoding the alpha9 nicotinic acetylcholine receptor (nAChR) subunit, results in abnormal synaptic terminal structure. Additionally, all nAChR-mediated cochlear activity is lost, as characterized by a failure of the descending efferent system to suppress cochlear responses to sound. In an effort to characterize the molecular mechanisms underlying the structural and functional consequences following loss of alpha9 subunit expression, we performed whole-transcriptome gene expression analyses on cochleae of wild type and alpha9 knockout (alpha9(-/-)) mice during postnatal days spanning critical periods of synapse formation and maturation.Data revealed that loss of alpha9 receptor subunit expression leads to an up-regulation of genes involved in synaptic transmission and ion channel activity. Unexpectedly, loss of alpha9 receptor subunit expression also resulted in an increased expression of genes encoding GABA receptor subunits and the GABA synthetic enzyme, glutamic acid decarboxylase. These data suggest the existence of a previously unrecognized association between the nicotinic cholinergic and GABAergic systems in the cochlea. Computational analyses have highlighted differential expression of several gene sets upon loss of nicotinic cholinergic activity in the cochlea. Time-series analysis of whole transcriptome patterns, represented as self-organizing maps, revealed a disparate pattern of gene expression between alpha9(-/-) and wild type cochleae at the onset of hearing (P13), with knockout samples resembling immature postnatal ages.We have taken a systems biology approach to provide insight into molecular programs influenced by the loss of nicotinic receptor-based cholinergic activity in the cochlea and to identify candidate genes that may be involved in nicotinic cholinergic synapse formation, stabilization or function within the inner ear. Additionally, our data indicate a change in the GABAergic system upon loss of alpha9 nicotinic receptor subunit within the cochlea

Surgical treatment of abdominal aortic aneurisms

Secția Chirurgie Vasculară IMSP SCR, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011În secția chirurgie vasculară a IMSP SCR, pe parcursul anilor 1988-2010 au fost operați 224 pacienți cu anevrisme ale aortei abdominale. SCa criteriu diagnostic pentru anevrism s-a considerat dilatarea aortei abdominale cu două diametre şi mai mult. Vârsta pacienților a fost cuprinsă între 15 şi 89 ani. Din totalul de pacienți 79,5%(178) au fost bărbați şi 20,5%(46) femei. La 18,75%(42) pacienți anevrismele au fost complicate prin ruptură completă sau incompletă, fiind operați în regim de urgență imediată. Etiologia a fost: ateroscleroza - 94,65% (212), aortoarteriita nespecifică - 3,57% (8), sindromul Marfan - 1,78% (4). Diagnosticul a fost stabilit clinic, ultrasonografic, prin Duplex vascular, angio-CT, aortografie, RMN. În 3 cazuri (1,34%) anevrismul implica şi arterele renale. Doi pacienți, neincluşi în studiu, au decedat preoperator prin hemoragie masivă cauzată de ruptura spontană a anevrismului în duoden şi cavitatea abdominală liberă. Toți pacienții au fost supuşi rezecției anevrismului aortal cu protezare aorto-distală (aortală, biiliacă, ilio-femurală, bifemurală), iar în 3 cazuri cu replantarea arterelor renale şi viscerale. Mortalitatea în anevrismele rupte a fost 57% (24), iar în cele complicate - 8% (18). Concluzii: pe parcursul ultimilor 5 ani a crescut ponderea pacienților cu anevrisme simptomatice sau deja complicate prin ruptură, astfel că toți pacienții cu factori de risc trecuți de 50 ani trebuie supuşi screening-ului prin USG sau Dopplerografie. Mortalitatea postoperatorie în anevrismele rupte s-a micşorat cu 13 %, iar în cele operate programat cu 7,55%. Implimentarea metodei endovasculare ar permite reducerea substanțială a acestui indice, mai ales în cazul anevrismelor complicate prin ruptură.During the period of 1988 - 2010, 224 patients underwent surgery for abdominal aortic aneurisms. The main diagnostic criteria was dilatation of the abdominal aorta by two diameters and more. All patients were aged between 15 and 89. Of all patients 79,5% (178) were males and 20,5% (46) were female. In 18,75% (42) cases, a complete or incomplete rupture of the aneurisms occurred. These patients underwent urgent surgery. Etiology: atherosclerosis – 94,65% (212), nonspecific aortoarteritis – 3,57% (8), Marfan syndrome – 1,78% (4). The diagnosis was made by clinical findings, vascular Duplex scanning, angio-CT and MRI. In 3(1,34%) cases the aneurism involved the renal arteries. There were two lethal outcomes, one caused by spontaneous rupture of the aneurism in the duodenum and the second caused by rupture into the peritoneal cavity. These cases were not included in the study. All patients underwent aneurism resection with aortal –distal (aortic, biiliac, ilio-femural, bifemural) allografting, while in three cases reimplantation of the renal arteries was necessary. The mortality in cases of ruptured aneurisms consisted 57% (24), and in cases of uncomplicated aneurisms – 8% (18).Conclusions: During the last 5 years we observed a raise in the rate of symptomatic aneurisms, including those complicated with rupture. Aortic ultrasonography or dopplerography should be used as screening methods in all patients, with risk factors, that are aged 50 and more. Postoperative mortality in cases of ruptured aneurisms has decreased by 13%, while in cases of planned aneurism surgery by 7,55%. Implementation of endovascular techniques would reduce substantially these indices

Optimizing surgical techniques in extra-anatomical ilio-femoral bypasses

Scopul lucrării. Bypass-ul extraanatomic ilio-femural crossover este o procedura chirurgicala utilizată pentru revascularizarea segmentului aorto-femural, când intervențiile endovasculare nu sunt posibile, iar aplicarea unui bypass aorto sau ilio-femural este dificilă sau chiar imposibilă din cauza condițiilor tehnice sau a stării pacientului. Scopul este studierea rezultatelor precoce și tardive pentru favorizarea unor schimbări și implementarea unor gesturi tehnice în aplicarea bypass-urilor crossover ilio-femural, pentru a crea o geometrie cât mai fiziologică ce poate oferi o soluție durabilă pe termen lung. Materiale și metode. Pe parcursul anilor 2001-2022 au fost efectuate 142 bypass-uri crossover ilio-femurale. Rezultate. În perioada postoperatorie a fost un singur deces și s-au efectuat 3 amputații. Au fost analizate duplex scanările și CT angiografiile în primele 12 luni postoperatorii, pentru aprecierea altor leziuni aterosclerotice, care ar necesita revascularizare deschisă s-au endovasculară atît in bazinul recipient cât și cel donator. Totodată, a fost apreciata poziția și forma bypass-ului ce a dus la folosirea ulterioară a unor noi procedee tehnice ce diferă de cele descrise anterior. Concluzii. Optimizarea tehnicilor chirurgicale creând o geometrie cât mai fiziologică, excluderea maximală a angulărilor stenozante ale grefei poate oferi bypass-ului extraanatomic crossover ilio-femural o durabilitate îndelungată. Acest lucru poate favoriza creșterea frecvenței indicațiilor la folosirea bypass-urilor crossover ilio-femural.Aim of study. The extra-anatomic ilio-femoral crossover bypass is a surgical procedure used for revascularizing the aorto-femoral segment when endovascular interventions are not possible, and when applying an aorto- or ilio-femoral bypass is difficult or even impossible due to technical conditions or the patient's condition. The aim was to study the early and late outcomes to promote changes and implement technical gestures in the application of ilio-femoral crossover bypasses, aiming to create a more physiological geometry that can provide a durable long-term solution. Materials and methods. Between 2001 and 2022, a total of 142 ilio-femoral crossover bypasses were performed. Results. There was one death and three amputations in the postoperative period. Duplex scans and CT angiography were analyzed in the first 12 months postoperatively to assess other atherosclerotic lesions that would require open or endovascular revascularization in both the recipient and donor areas. Additionally, the position and shape of the bypass were evaluated, leading to the subsequent use of new technical procedures that differ from those previously described. Conclusions. Optimizing surgical techniques by creating a more physiological geometry and minimizing stenotic angles of the graft can provide the extra-anatomic ilio-femoral crossover bypass with long-lasting durability. This may increase the frequency of indications for using ilio-femoral crossover bypasses

Review of experience of family medicine in Europe and Central Asia : Executive summary

This report summarizes the findings of four case studies that review the experience of family medicine in Europe and Central Asia (ECA) Region. It is part of a study comprising five volumes that review the experience of family medicine in four countries in ECA--Armenia, Bosnia and Herzegovina, Kyrgyz Republic and Moldova. The report reviews the experience, draws lessons, and establishes an evidence base for detailed analysis. The study presents best practices for policy dialogue and future investments by the World Bank and other financial institutions. The detailed case studies compare these countries and draw common themes and issues. Comparisons are made with best-developed or existing models in the OECD and other countries in the Europe and Central Asia Region that have already undertaken family medicine reform

Calibration and Characterization of the IceCube Photomultiplier Tube

Over 5,000 PMTs are being deployed at the South Pole to compose the IceCube neutrino observatory. Many are placed deep in the ice to detect Cherenkov light emitted by the products of high-energy neutrino interactions, and others are frozen into tanks on the surface to detect particles from atmospheric cosmic ray showers. IceCube is using the 10-inch diameter R7081-02 made by Hamamatsu Photonics. This paper describes the laboratory characterization and calibration of these PMTs before deployment. PMTs were illuminated with pulses ranging from single photons to saturation level. Parameterizations are given for the single photoelectron charge spectrum and the saturation behavior. Time resolution, late pulses and afterpulses are characterized. Because the PMTs are relatively large, the cathode sensitivity uniformity was measured. The absolute photon detection efficiency was calibrated using Rayleigh-scattered photons from a nitrogen laser. Measured characteristics are discussed in the context of their relevance to IceCube event reconstruction and simulation efforts.Comment: 40 pages, 12 figure

Search for Supernova Relic Neutrinos at Super-Kamiokande

A search for the relic neutrinos from all past core-collapse supernovae was conducted using 1496 days of data from the Super-Kamiokande detector. This analysis looked for electron-type anti-neutrinos that had produced a positron with an energy greater than 18 MeV. In the absence of a signal, 90% C.L. upper limits on the total flux were set for several theoretical models; these limits ranged from 20 to 130 nu_e bar cm^-2 s^-1. Additionally, an upper bound of 1.2 nu_e bar cm^-2 s^-1 was set for the supernova relic neutrino flux in the energy region E_nu > 19.3 MeV.Comment: 4 pages, 2 figures. Submitted to Physical Review Letters. New version includes corrections to Figure 1. Also, text has been shortened to conform with the space limitations of PR

Solar 8B and hep Neutrino Measurements from 1258 Days of Super-Kamiokande Data

Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0-20.0MeV. The measured solar neutrino flux is 2.32 +- 0.03(stat.) +0.08-0.07(sys.)*10^6cm^{-2}s^{-1}, which is 45.1+-0.5(stat.)+1.6-1.4(sys.)% of that predicted by the BP2000 SSM. The day vs night flux asymmetry is 0.033+-0.022(stat.)+0.013-0.012(sys.). The recoil electron energy spectrum is consistent with no spectral distortion (\chi^2/d.o.f. = 19.0/18). The seasonal variation of the flux is consistent with that expected from the eccentricity of the Earth's orbit (\chi^2/d.o.f. = 3.7/7). For the hep neutrino flux, we set a 90% C.L. upper limit of 40 *10^3cm^{-2}s^{-1}, which is 4.3 times the BP2000 SSM prediction.Comment: 7 pages, 5 figures, submitted to PRL (part of this paper

Search for Dark Matter WIMPs using Upward Through-going Muons in Super-Kamiokande

We present the results of indirect searches for Weakly Interacting Massive Particles (WIMPs) with 1679.6 live days of data from the Super-Kamiokande detector using neutrino-induced upward through-going muons. The search is performed by looking for an excess of high energy muon neutrinos from WIMP annihilations in the Sun, the core of the Earth, and the Galactic Center, as compared to the number expected from the atmospheric neutrino background. No statistically significant excess was seen. We calculate flux limits in various angular cones around each of the above celestial objects. We obtain conservative model-independent upper limits on WIMP-nucleon cross-section as a function of WIMP mass and compare these results with the corresponding results from direct dark matter detection experiments.Comment: 10 pages, 14 figures, Submitted to Phys. Rev.