Orli Sagi

p66ShcA and ageing: modulation by longevity-promoting agent aurintricarboxylic acid

Many mutations that extend the lifespan of the lower organisms such as C. elegans and Drosophila, are associated with signaling or apoptotic pathways. Recently, such a possibility was shown in mammals: p66ShcA-deficient mice were more resistant to oxidative stress and lived longer than the wild-type animals [Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Randolfi, P.P., Lanfrancone, L., Pelicci, P.G., 1999. The p66Shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402, 309-313]. There is evidence to implicate p66ShcA in age-related degenerative pathology, including atherosclerosis, sarcopenia, and Alzheimers disease. We hypothesized that a low level expression of p66ShcA could be associated with longevity. Also, we suggested that the level of p66ShcA could be modulated by a putative longevity-promoting agent aurintricarboxylic acid [aurintricarboxylic acid (ATA); Fraifeld, V., Wolfson, M., Sagi, O., Seidman, R., Asraf, H., Utko, N., Muradian, K., 2002. Effects of anti-apoptotic agent aurintricarboxylic acid on longevity and longevity-associated processes. Biogerontology 3, 48]. We have found that: (i) the level of p66ShcA decreases with advanced age. Thirty-six-month-old mice have the lowest, whereas newborns have the highest p66ShcA levels; (ii) ATA significantly decreases the p66ShcA level in mouse lungs. In addition, the lifespan-prolongation effect of ATA in a Drosophila model was further validated. The results support the suggested role for the p66ShcA as one of the lifespan determinants in mammals; p66ShcA therefore represents a potential target for pharmacological longevity-promoting intervention.

Dramatic increase in laboratory-diagnosed human cutaneous leishmaniasis cases in southern Israel, 2007–2013

Abstract Background: Cutaneous leishmaniasis (CL) is an endemic zoonosis in southern Israel. In recent years, substantial urbanization has been taking place in this region. The introduction of populations into endemic foci was previously reported to facilitate human CL outbreaks. Our aim was to describe a continuous CL outbreak in southern Israel, through laboratory reports of CL diagnosis. Methods: The Soroka University Medical Center parasitology laboratory is the major laboratory confirming CL cases in our region. Data regarding patients referred to the hospital for CL diagnosis were collected retrospectively. Cases were defined by microscopic findings of skin lesion biopsies. Results: The annual number of cases sent for CL laboratory confirmation increased from a mean of 77 ± 9 in the years 2007–2010 to 178, 327, and 528 in the years 2011, 2012, and 2013, respectively. The respective increase in annual confirmed/positive cases of CL was from 36 ± 12 to 117, 171, and 282, leading to respective increase in CL rate (per 100 000) from 5.8 ± 1.9 to 18.4, 26.3, and 42.7. The outbreak was mainly (> 60%) observed in the north-west area of the region. Conclusions: In conclusion, a sevenfold increase in laboratory-confirmed CL was observed in southern Israel in 2007–2013, probably reflecting a bigger outbreak, possibly related to urban expansion bordering with CL foci.

Volatile organic compounds generated by cultures of bacteria and viruses associated with respiratory infections

Respiratory infections (RI) can be viral or bacterial in origin. In either case, the invasion of the pathogen results in production and release of various volatile organic compounds (VOCs). The present study examines the VOCs released from cultures of five viruses (influenza A, influenza B, adenovirus, respiratory syncitial virus and parainfluenza 1 virus), three bacteria (Moraxella catarrhalis, Haemophilus influenzae and Legionella pneumophila) and Mycoplasma pneumoniae isolated colonies. Our results demonstrate the involvement of inflammation-induced VOCs. Two significant VOCs were identified as associated with infectious bacterial activity, heptane and methylcyclohexane. These two VOCs have been linked in previous studies to oxidative stress effects. In order to distinguish between bacterial and viral positive cultures, we performed principal component analysis including peak identity (retention time) and VOC concentration (i.e. area under the peak) revealing 1-hexanol and 1-heptadecene to be good predictors.

Cystic echinococcosis in Southern Israel

The aim of this retrospective, population-based study was to characterize demographically and clinically cystic-echinococcosis (CE) in southern Israel, between 2005 and 2012. Newly-diagnosed (nd-CE) and past-diagnosed (pd-CE, diagnosed before the study) cases were defined. Two populations live in southern-Israel, receiving medical treatment at a single hospital: the Jewish and the Bedouin populations (resembling resource-rich and resource-poor populations, respectively). 126 CE cases were identified; 55 nd-CE and 71 pd-CE. Mean annual nd-CE incidence per 100,000 in the Bedouin and Jewish populations were 2.7 ± 1.2 and 0.4 ± 0.3, respectively (P<0.001). None of the Bedouin and 86.5% of the Jewish patients were born outside Israel. Liver and lung involvement were recorded in 85.7% and 15.1% of overall-CE, respectively. Abdominal pain, cough, fever, eosinophilia and asymptomatic disease were documented in 63.6%, 32.7%, 27.3%, 41.5% and 12.7% of nd-CE, respectively. Serology sensitivity for first test and any positive test were 67.3% and 83.3%, respectively. Computed tomography, ultrasonography and X-ray diagnosis were documented in 79.2%, 58.4% and 17.0% of overall-CE, respectively, with ultrasonography mainly used in liver-CE and X-ray in lung-CE. Treatment included surgery and albendazole in 50.0% and 55.3% of CE, respectively. We conclude that CE is endemic in southern-Israel among the Bedouin population, while disease is probably mainly imported in the Jewish population. Liver involvement and eosinophilia rates were high compared with those of other endemic regions, possibly due to differences in the timing of diagnosis. These findings may help developing treatment and prevention strategies.

Cutaneous leishmaniasis caused by Leishmania infantum in Southern Israel.

Cutaneous leishmaniasis (CL) caused by Leishmania major is common in southern Israel, while Leishmania infantum (sub-strain of L. donovani, causing zoonotic visceral leishmaniasis) infections were rarely reported in Israel and only in other regions. We report the first case of L. infantum infection in southern Israel, presented atypically as CL in an immunosuppressed 47-year old male. The patient was treated with liposomal amphotericin-B and recovered, without extra-cutaneous complications. Diagnosis of L. infantum CL was confirmed by microscopic identification of amastigotes in Gimsa-stained smear of skin lesion, positive blood serology and a positive polymerase chain reaction (PCR) amplification of the internal transcribed spacer 1 genes (ITS1) and restriction fragment length polymorphism (ITS1 PCR-RFLP). We also review the medical literature on old- world CL caused by L. infantum. Multiple L. donovani/infantum CL cases were identified in the literature search. These can be divided schematically to two: 1) In several endemic countries, L. infantum strains are the main causative agents of CL; 2) In other regions, CL is almost exclusively caused by L. major or L. tropica, while L. donovani strains CL cases were reported sporadically or as imported disease.

Differences in prevalence of parasites in stool samples between three distinct ethnic pediatric populations in southern Israel, 2007-2011.

Intestinal parasites cause significant morbidity worldwide, particularly in developing populations. At least three pediatric populations reside in southern Israel: the Bedouin population, the general Jewish population and Jewish children of Ethiopian origin. Our aim was to compare intestinal parasite prevalence between the three pediatric populations in southern Israel. This is a retrospective, laboratory, population-based surveillance. Most ova and parasite (O&P) tests in southern Israel (hospital and community obtained) are performed by the hospital parasitology laboratory. All pediatric stool O&P tests examined by the hospital laboratory between 2007 and 2011 were included. Overall, 45,978 samples were examined; 27,354, 16,969 and 1655 from Bedouin, non-Ethiopian Jewish and Ethiopian children, respectively. 16,317 parasites were identified in 12,325 (26.8%) positive samples. Total prevalences were 36%, 11% and 46% for Bedouin, non-Ethiopian Jewish and Ethiopian children, respectively. Blastocystis hominis, Giardia lamblia and Entamoeba species were the most common parasites identified, constituting ≥80% of positive samples in all groups. Hymenolepis nana was rarely identified in non-Ethiopian Jewish children (0.04% of isolates compared with 2.6% and 0.5% in Bedouin and Ethiopian children, respectively). Other helminths, excluding H. nana and Enterobius vermicularis, were identified almost exclusively in Ethiopian children ≥5years of age. In conclusion, the Bedouin and Ethiopian children were characterized by higher parasite prevalence in stool, compared with the non-Ethiopian Jewish children, probably reflecting higher intestinal parasitic disease rates. Certain helminthic infections were identified almost exclusively in the Ethiopian children. These differences may be associated with lifestyle differences between the three populations.

Sensitive Molecular Diagnostics for Cutaneous Leishmaniasis

Abstract Background Rapid diagnosis of cutaneous leishmaniasis (CL) and identification of Leishmania species is highly important for the disease management. In Israel, CL is caused mainly by Leishmania major and Leishmania tropica species. Methods We established an easy to handle point of care lesion-swabbing, combined with a highly sensitive multiplex real time PCR (multiplex qPCR) for accurate and rapid diagnosis of Leishmania species. Results Using three probes: one general for: Leishmania species, and two specific for L major, and L tropica, we screened 1783 clinical samples collected during two years. Leishmania species was found in 1086 individuals, 1008 L major, and 70 L tropica. Eight samples positive for Leishmania species only, were further tested using a second set of multiplex qPCR developed, and were found positive for Leishmania braziliensis and Leishmania infantum/donovani (2 and 6 samples, concomitantly). Conclusions Taken together, the test enabled diagnostics and better treatment of Leishmania infections from the Old World (1078 samples) and the New World (8 samples), and the subtyping of the dominant strains in the region, as well as in returning travelers’.

ShcC proteins: brain aging and beyond.

To date, most studies of Shc family of signaling adaptor proteins have been focused on the near-ubiquitously expressed ShcA, indicating its relevance to age-related diseases and longevity. Although the role of the neuronal ShcC protein is much less investigated, accumulated evidence suggests its importance for neuroprotection against such aging-associated conditions as brain ischemia and oxidative stress. Here, we summarize more than decade of studies on the ShcC expression and function in normal brain, age-related brain pathologies and immune disorders with a focus on the interactions of ShcC with signaling proteins/pathways, and the possible implications of these interactions for changes associated with aging.

Dissemination of the Methicillin Resistant Staphylococcus aureus (MRSA) Pediatric Clone (ST5-T002-IV-Pvl+) as a Major Cause of Community Associated (CA) Staphylococcal Infections in Bedouin Children, Southern Israel

Abstract Background Pediatric CA-MRSA infections are emerging worldwide. High CA-MRSA carriage rates were previously described in healthy Bedouin children (Adler et al, J Clin Microbiol 2009). We assessed demographic, clinical and molecular characteristics of MRSA infections in children in southern Israel. Methods Soroka University Medical Center microbiology laboratory serves the entire population of southern Israel, divided into two ethnic groups, Bedouin and Jews. All in-hospital MRSA isolates from children 0–18 years, obtained in 2016 were included. Clinical data were recorded from the hospital’s computerized records. Health-care associated (HA) and community-associated infections were defined according to the US Center for Disease Control and Prevention. All isolates were evaluated for staphylococcal cassette chromosome (SCCmec), Panton–Valentine leucocidin (PVL), Staphylococcus aureus protein A (spa) type as well as by pulsed-field-gel-electrophoresis (PFGE) and antimicrobial susceptibility testing. Results Overall 95 (18%) of S. aureus isolates were MRSA (Table 1). Twenty-five different MRSA strains were identified. 28 isolates (29.5% of all MRSA) belonged to a pediatric clone, rarely observed in Israel (SCC IV, PVL positive, spa type 002; all demonstrate identical PFGE fingerprints). 82% of infections caused by this clone were community-acquired and were mainly observed in young Bedouin children, causing skin and soft-tissue infections (SSTI). Comparisons between the new clone and other CA-MRSA and HA-MRSA strains are shown in Table 1. All isolates of the pediatric clone were susceptible to TMP/SMX, ciprofloxacin, gentamicin, tetracycline, rifampicin and vancomycin; 17.8% were nonsusceptible to erythromycin and clindamycin (Table 2). Conclusion The pediatric CA-MRSA clone, previously described only in sporadic cases in Israel, is emerging among previously healthy, young Bedouin children, typically causing SSTI. Isolates are susceptible to a variety of non-β lactam antibiotics. Disclosures All authors: No reported disclosures.