Qatar Foundation Annual Research Conference Proceedings Volume 2016 Issue 1

Background

Studies show that diabetics are in high risk for complications, hospitalization, and death from uncontrollability.

Good Glycemic control is an important part of preventive services for diabetic complications. One of the most important treatment options for Diabetic patient is insulin therapy, however there is evidence of poor physician knowledge about types and modalities of insulin therapy. Lack of knowledge will increase the likelihood of medication errors; contribute to poor glycemic control in diabetic patient and increased morbidity and mortality

- Our aim is to improve Insulin therapy related knowledge in type 2 DM Among Physicians in West-bay health center by 20% above baseline by January 2013 and To raise the awareness of that problem among our physicians.

Subjects, Materials & Methods

- The project began on November 2012 with baseline Questionnaire survey as pilot for our study. Followed by This Pre-intervention insulin knowledge Questionnaire conducted to Identify deficient areas in the insulin-Related knowledge with the results showed Mean Percentage of incorrect answers is 62%.

- For more on which brainstorming session was done to identify the root causes of such problem, and depicted using the fish bone diagram.

- A survey questionnaire was designated to assess the main causes of the problem and distributed to nurses and physicians working in NCD clinics.

Prioritization of Reasons of insufficient insulin therapy knowledge demonstrated in Paretto chart.

According to analysis we found three main causes of the problem:

1. a – No Training Program for physicians.

2. No specific form or Ineffective Auditing

3. Less Exposure to Patient with T2DM.

- Our intervention was in the form of:

1- Training program: conducted on December 2012 and it is include a PowerPoint presentation, problems solving cases, and group discussion about insulin types and Pharmacokinetics, concerns about insulin therapy, initiation, titration, and monitoring of insulin therapy, and insulin regimens in PHC setting.

2- Post intervention insulin knowledge Questionnaire: distributed after conducting training program.

- Two audits done retrospectively before intervention & one done after to show average percentage of improvement in knowledge to assess effect of intervention.

- All data was demonstrated using run chart.

Results

Improvement of insulin therapy-related knowledge reflected by mean percentage of correct answers in pre & post questionnaire conducting before and after training program. showed mean correct answers improved from 38% to 78 % in physician in West Bay H.C.

Conclusions

The results of the pre and post questionnaire analyses clearly showed an improvement in the level of insulin therapy knowledge among physicians.

The study indicates the areas that need to be addressed with greater emphasis.

The post test analysis shows that the training program has been successful in significantly improving knowledge of insulin therapy that may help to improve patient safety in PHC.

Next Steps

Share results with training and development dept.

Expansion of insulin therapy training program to include All PHC to transfer the knowledge.

Continue process of education (twice annually).

To analyses the segmented data to see where the improvement can be happen.

The novel Schiff bases I HAMTTSC (2-Acetyl-4-methylthiazole thiosemicarbazone), II HAPTSC(2-Acetylpyrazine thiosemicarbazone) and their complexes with Pt(II) and Pd(II): 1 [Pt(AMTTSC)Cl], 2 [Pt(AMTTSC)2], 3 [Pd(AMTTSC)Cl], 4 [Pd(AMTTSC)2], 5 [Pt(APTSC)Cl], 6 [Pt(APTSC)2], 7 [Pd(APTSC)Cl], and 8 [Pd(APTSC)2] have been synthesized, and characterized by elemental analysis and spectroscopic studies. The crystal structure of the Schiff bases I, II, and the complex 1 [Pt(AMTTSC)Cl], have been solved by single-crystal X-ray diffraction. The electronic, IR, UV/Vis, and NMR spectroscopic data of I and II and their complexes are reported. The in vitro antitumor activity of the Schiff bases and 1, 2, 4, 5 and 6 complexes against two different human tumor cell lines (HT-29 and HuTu-80) reveals that the complexes are more cytotoxic than their corresponding ligands with IC50 values at the range of 0.1–10 μM. These compounds can therefore be considered as agents with potential antitumor activity.

Molecular structure of 1 [Pt(AMTTSC)Cl]

Introduction

Thiosemicarbazones (TSCNs) are very promising molecules in coordination chemistry because of their pharmacological properties of both ligands and complexes, (1–3) which include notably their antiparasital, (4) antibacterial (5, 6) and antitumor activities (7) depending on the parent aldehyde and ketone and, of course, metal ion. The thiosemicarbazone ligand usually coordinates with a metal through the imine nitrogen and the sulphur atom forming a five-membered ring chelate. Since cis-platin emerged as the most important antitumor drug (8), thousands of metal complexes have been synthesized and characterized in order to study the effect of the metal, the attached group on the structural and kinetic properties involved in the biological activity. (9) However significant problems are still extant, including side effects, toxicity, cancer specificity and acquired resistance. Consequently the development of new compounds outside the usual coordination sphere or of different structural properties is the challenge to cancer research.

Synthesis of the ligands

The ligands 2-Acetyl-4-methylthiazole thiosemicarbazone and 2-acetylpyrazine thiosemicarbazone, were prepared according to the literature (10).

Synthesis of Complexes Pt (AMTTSC)Cl Complex

A solution of K2PtCl4 (0.208 g, 0.5 mmol) in methanol, was added dropwise to a stirred solution of HAMTTSC (0.5 mmol) in 20 mL of methanol. The solution was refluxed for 2 hours and stirred for 24 hours at room temperature. The dark red precipitate was collected by filtration and dried in vacuo. Crystals suitable for X-Ray diffraction were obtained through slow evaporation of the DMF solvent.

Solid, yield: 70.59%, m.p. 236–237°C. Anal. Calc. For Pt(C7H9N4S2)Cl (443.84 g/mol): C, 18.94%; H, 2.04%; N, 12.62%. Found: C, 18.74%; H, 2.18%; N, 12.85%. I.R. (solid state, cm^− 1): ν(NH2) 3395, 3267; ν(C = N) 1520.38; ν(C = S) 873.31; ν(N-N)1065.89. 1H-N.M.R (DMSO-d6): δ 2.21, 2.41 (s, 6H, 2CH3), 7.75 (s, 1H); 8.07(b, 2H, NH2).). 13C-N.M.R. (DMSO-d6): δ 13.93, 16.39 (2CH3); 148.59,-154.62(3C ring); 171.92 (HC = N); 183.20 (C = S). Electronic spectra (λmax nm): 270, 391, 531.

Pt (AMTTSC) 2 Complex

A solution of K2PtCl4 (0.208 g, 0.5 mmol) in methanol, was added dropwise to a stirred solution of HAMTTSC (1.0 mmol) in 30 mL of methanol. The solution was refluxed for 2 hours and stirred for 24 hours at room temperature. The pinkish red precipitate was collected by filtration and dried in vacuo.

Solid, yield: 74.36%, m.p. dec.>245°C.Anal. Calc. For Pt(C7H9N4S2)2 (621.69 g/mol): C, 27.05%; H, 2.92%; N, 18.02%. Found: C, 27.01%; H, 3.028%; N, 18.97%. IR (solid state, cm^–1): ν(NH2) 3354.48, 3265.78; ν(C = N) 1535.94; ν(C = S) 873.25; ν(N-N) 1075.01. 1H-N.M.R (DMSO-d6): δ 2.21, 2.39 (s, 6H,2CH3), 7.74, 7.34(s, 1H); 8.07 (b, 2H, NH2); 8.51, (b, 2H, NH2). 13C-N.M.R. (DMSO-d6): δ 13.51, 16.39 &13.91, 16.76 (4CH3); 144.02-152.49 &148.57-154.64 (3C ring); 166.07&171.93 (HC = N); 183.22 (C = S). Electronic spectra (λmax nm): 270, 363, 389, 53.

Pd (AMTTSC)Cl Complex

A solution of K2PdCl4 (0.163 g, 0.5 mmol) in methanol, was added dropwise to a stirred solution of HAMTTSC (0.5 mmol) in 20 mL of methanol. The solution was refluxed for 2 hours and stirred for 14 hours at room temperature. The orange precipitate was collected by filtration, washed with ethanol and ether, and dried in vacuo.

Solid, yield: 92.39%. m.p. 236–237°C. Anal. Calc. For Pd(C7H9N4S2)Cl (355.18 g/mol): C, 23.67%; H, 2.55%; N, 15.77%. Found: C, 22.94%; H, 2.68%; N, 15.09%. IR (solid state, cm^− 1): ν(NH2) 3426.47, 3304.62; ν(C = N) 1552.37; ν(C = S) 867.85; ν(N-N) 1118.21. 1H-N.M.R. (DMSO-d6): δ 2.25, (s, 6H, 2CH3), 7.64 (s, 1H); 7.93 (d, 2H, NH2).13C-N.M.R. (DMSO-d6): δ 13.83, 16.36 (2CH3); 145.69, 147.79–154.36(3C ring); 169.58 (HC = N); 180.71 (C = S). Electronic spectra (λmax nm): 274, 313, 386,493.

Pd(AMTTSC)2 Complex

A solution of Pd(acac)2 (0.152 g, 0.5 mmol) in CH2Cl2/ CH3OH (30 mL, 2:1 v/v) was added dropwise to a stirred solution of HAMTTSC (1.0 mmol) in 30 mL of methanol. The solution was refluxed for 2 hours and stirred for 24 hours at room temperature. The red precipitate was collected by filtration, washed with ethanol and ether, and dried in vacuo.

Solid, yield: 79.54%. m.p. dec.>174°C. Anal. Calc. For Pd(C7H9N4S2)2, (533.03 g/mol): C, 31.55%; H, 3.4%; N, 21.02%. Found: C, 30.77%; H, 3.62%; N, 19.84%. IR (solid state, cm^− 1): ν(NH2) 3308.98, 3257.77; ν(C = N) 1557.07; ν(C = S) 871.65; ν(N-N)1080.62. 1H-N.M.R. (DMSO-d6): δ 1.46, 1.62 (s, 6H, 2CH3), 7.04 (s, 1H); 8.04, 6.74 (d, 2H, NH2). 13C-N.M.R. (DMSO-d6): δ 13.66, 16.18 (2CH3); 147.49, 152.70& 148.44, 155.45 (3C ring); 169.62&171.19 (HC = N);, 182.38 (C = S). Electronic spectra (λmax nm): 289, 348, 448.

Conclusion

New potential anti-cancer Pt (II) and Pd(II) complexes were synthesized through the reaction of the heterocyclic thiosemicarbazone ligands with Pt (II) and Pd (II) ions in 1:1 and 1:2 ratios reactions.

The structures of the synthesized compounds were elucidated on the bases of spectroscopic data (IR. 1H and 13C N.M.R, UV-VIS and XRD).

As the experimental results show, the synthesized Schiff bases reacts with Pt(II) ion in different modes of bonding, they react as tridentate through the mercaptide sulfur ion, the azomethine nitrogen atom and the nitrogen of the ring.

All ligand and complexes tested show a concentration dependent reduction of cell proliferation. The test results show that the change of the ligand metal ratio has significant effects on the antiproliferative activities of the platinum(II) complexes. In general, it was found that complexes were more active than the corresponding ligand. The complex with the formula PtLCl was found to be slightly more active than the complexes with formula PtL2 against HT-29 and HuTu cancer cells line.

References

(1) Kovala-Demertzi D., Boccarelli A., Demertzis M. A., and Coluccia M., In vitro antitumor activity of 2-acetyl pyridine 4N-ethyl thiosemicarbazone and its platinum(II) and palladium(II) complexes, Chemotherapy, (2007), 53,2, 148.

(2) Kovala-Demertzi D., Varadinova T., Genova P., Souza P., and Demertzis M. A., “Platinum(II) and palladium(II) complexes of pyridine-2-carbaldehyde thiosemicarbazone as alternative antiherpes simplex virus agents, Bioinorganic Chem. and App, (2007), 56165, 2007.

(3) Scovill, J.P. Klayman D.L., Franchino C.F., Acetylpyridine Thiosemicarbazones Complexes with Transition Metals as Antimalarial and Antileukemic Agents. J. Med. Chem., (1982); 25, 1261.

(4) Duffy K. J., Shaw A. N., Delmore E., Dillon S. B., Erickson-Miller C., Giampa L., Huang Y., Keenan R. M., Lamb P., Liu N., Miller S. G., Price A. T., Rosen J., Simth H., Wiggal K. J., Zhang L, Luengo J. I., J. Med. Chem., (2002), 45, 3573.

(5) Agarwal R. K., Singh L., and Sharma D. K., Synthesis, spectral, and biological properties of copper(II) complexes of thiosemicarbazones of Schiff bases derived from 4-aminoantipyrine and aromatic aldehydes, Bioinorg. Chem. and Appl., (2006), 59509, 2006.

(6) Pandey O. P., Sengupta S. K., Mishra M. K., and Tripathi C. M., Synthesis, spectral and antibacterial studies of binuclear titanium(IV)/zirconium(IV) complexes of piperazine dithiosemicarbazones, Bioinorg. Chem. and Appl, (2003), 1., 1, 35.

(7) Quiroga A. G., Pérez J. M., López-Solera I., et al., Novel tetranuclear orthometalated complexes of Pd(II) and Pt(II) derived from p isopropylbenzaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP resistant tumor cell lines. Interaction of these complexes with DNA, J. of Med. Chem, (1998), 41, 9, 1399.

(8) Smith J. E., Talbot D. C., Ber. J. Cancer, (1991), 65, 787.

(9) Hacker M. P., Khokar A. R., Brown D. B., McCormack J. J., Krakoff J. M., Cancer Res, (1985), 45, 4748.

(10) De Lima G.M., Neto J.L., Beraldo H., Seibald H.G.L, Duncalf D.J.,J.of Molec.Struc.(2001), 604, 287.

Pulmonary tuberculosis (PTB) is a common worldwide infection and a medical and social problem causing high mortality and morbidity, especially in developing countries. An expert system for diagnosis of this disease was designed based on expert's knowledge for providing decision support platform to assist fresh graduator (inexperienced) physicians, and other healthcare practitioners to arrive the final diagnosis of TB more quickly and efficie ntly especially in rural areas. Information about pulmonary tuberculosis and its symptoms and treatment from doctor who are specializing in the diagnosis and treatment of tuberculosis were collected.

The system was built using C sharp language and artificial intelligence based expert system in coordinated manner help in the diagnosis of tuberculosis disease and assistance in giving the necessary treatment In addition to giving advice to patients.

Background and Objectives

Renal cell carcinoma is the most common and lethal form of all renal cancers, and accounts for 4.1% of all cancer cases in Qatar. Mutations to Von-Hippel Lindeau (VHL) gene in renal cells activates hypoxia inducible factor-1 alpha (HIF-1α) response pathway, and contributes to increased proliferation and progression to renal cell carcinoma. Hence, chemotherapeutic modalities available to treat renal cell carcinoma are targeted toward modulation of the VHL-HIF response pathway. Annonacin, a potent cytotoxic mono-tetrahydrofuran acetogenin found in Annonaceae plants, has been demonstrated to exert anticancer activity against breast cancer; however, its therapeutic potential against renal cell carcinoma is yet to be determined. Hence the objective of this study is to investigate anti-neoplastic potential of annonacin in renal carcinoma cells.

Methods

We investigated the effect of annonacin - at concentrations ranging from 0.5 to 2 μM – on cell viability (using MTT assay and Alamar blue assay), and the protein expression of markers of HIF signaling pathway (HIF-1α), mTOR pathway (Thr-389 phosphorylation of p70S6 kinase), cell cycle progression (p21 levels), and apoptosis (caspase-3 expression) in CaKi-2 cells, a human renal carcinoma cell line. The cells were treated with annonacin for 24 or 48 hours and assessed for the aforementioned parameters.

Results

hour annonacin treatment caused a significant and dose-dependent decrease in the viability of CaKi-2 cells, i.e., 42% in 0.5 μM, 36% in 1 μM and 29% in 2 μM annonacin treatment groups as compared to control set at 100%. This was further confirmed by Alamar blue assay, which revealed a significant decrease in the viability of CaKi-2 cells upon treatment with annonacin for 48 h. The expression of HIF-1α was reduced by 68% at 24 h in CaKi-2 cells treated with 2 μM annonacin. In addition, the expression of p21 (a key molecule that inhibits transition of cells from G1 to S phase in cell cycle) was induced by 1.34-fold in 0.5 μM annonacin-treated cells indicating an arrest in G1 phase of cell cycle. This was further confirmed through cell cycle analysis using Tali cytometer, in which annonacin treated groups (0.5 μM and 1 μM) showed cell cycle arrest at G1 phase, i.e., 57% of cells in G1 phase with 0.5 μM annonacin treated vs. 7% of cells in G1 phase in control group. In addition, a dose-dependent decrease in the phosphorylation of p70S6 kinase (a downstream target of mTOR) was observed with annonacin treatment at both 24 and 48 h end-points. This suggests that treatment of annonacin has possibly led to the inhibition of mTOR, in addition to suppression of HIF-1α activation, and underscores the cross-talk between HIF pathway and mTOR signaling pathway in renal cell carcinoma.

Conclusions

Our findings demonstrate that annonacin treatment (at concentrations ranging from 0.5 to 2 μM) inhibits HIF-1α and mTOR activation and causes cell cycle arrest at G1 phase and induces apoptosis in renal cell carcinoma. These findings indicate that annonacin exerts anti-cancer effects via modulation of HIF and mTOR signaling pathways, resulting in alterations in the cell cycle and activation of apoptosis in renal cell carcinoma. In conclusion, our study for the first time unveils the therapeutic potential of annonacin to inhibit the progression of renal cell carcinoma. Further studies in vivo are required to establish its efficacy to treat patients with renal cell carcinoma.

Funding Source

This study is supported by an intramural grant (#QUUG-CPH-CPH-14/15/7) funded by the Office of Academic Research, Qatar University, Doha, Qatar.

Purpose

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disease of the pulmonary vasculature that remains poorly understood. Despite a number of available FDA approved drugs, survival remains low, reaching an estimated 5-year survival as low as 27%. This severe disease is characterized by dysfunction and eventual failure of the right ventricle (RV) of the heart. The main focus of therapeutic strategies thus far has been to target the pathways of pulmonary vascular remodeling that lead to the hypertensive phenotype. It is not known however, if there is an added therapeutic benefit in targeting the RV directly. Prostacyclin analogues are among the most widely used therapies for PAH. However, it is unknown whether they confer protection exclusively via attenuating pulmonary vascular remodeling and constriction or if RV myocardio-specific mechanisms are also involved. Moreover, their use in severe models of PAH has not been adequately tested. Insight into these two major unknowns could not only blaze the trail of new effective therapies for PAH to improve survival, but would also open new avenues for targeting other major forms of heart failure. To address gaps in knowledge of the underlying responses to prostacyclin, the analogue treprostinil was used in a pre-clinical rat Sugen-hypoxia (SuHx) model of angioproliferative severe PAH that closely resembles the human disease.

Methods

Male Sprague-Dawley rats (300g) were implanted with ALZET osmotic pumps containing vehicle or treprostinil (900 ng/kg/min), injected concurrently with a bolus of Sugen (SU5416; 20 mg/Kg) and exposed to 3 wk hypoxia (10% O2) followed by 3 wk normoxia (21% O2). RV function was assessed using pressure-volume loops measured using an admittance catheter and hypertrophy assessed by Fulton Index (FI; RV/LV+Septum wet weight).

Results

Treprostinil significantly reduced SuHx-associated RV hypertrophy and rise in systolic pressure (FI: 0.26 ± 0.02, 0.58 ± 0.04 & 0.37 ± 0.05, P

Background

As a conventional type of communication, health education usually face several barriers that make its outcome fall short. Among many, lack of interest, distraction, and rejection are well documented barriers to engaging audience in a communication process leading to behavioral change. Despite the novel corona virus which was responsible for the Middle East Respiratory Syndrome (MERS-CoV) created public concerns, it, on the other hand, paved the road to effective health education via raising receivers’ attention. With the aim to highlight the context and factors attributed to educate the public during epidemics, this study documented how the outbreak of MERS-CoV offered valuable opportunities to communicate critical educational messages on the recommended preventive behaviors and practices.

Methods

In this retrospective study, we documented the timeline of MERS-CoV key events in Qatar, along with the disseminated health education messages that were captured by the print media during the period Sep 2012 through Nov 2013.

Results

The media documented that one of the first two reported cases worldwide was a Qatari national. A significant turn of the public's risk perception about MERS-CoV took place when studies documented that camels are thought to play critical role in the virus transmission to humans. Six months after the identification of the first case, this relationship was confirmed when it was declared that the MERS-CoV was isolated from camels in Qatar, provided that raising camels is a social norm and an embedded cultural practice in the country and across the region. Nevertheless, MERS-CoV cases and deaths continued to be reported.

Out of 153 news stories reported on MERS-CoV, 12 major developments either reporting confirmed cases or deaths were identified in Qatar. Two Press conferences, sixteen press releases, and two interviews were counted, all from competent authorities. As the novel virus captured the media attention, all aspects of the new virus were extensively reported, ranging from the basic information about the virus traits, the clinical signs and symptoms, treatment outcome of cases, to the ongoing researches, epidemiological findings of the most vulnerable persons, the zoonotic nature of the disease, and the recommended course of action. The public pressing demand for updates and information drove the media interest to arrange talk shows and interviews with the high health officials to give firsthand accounts about the virus and the prevention and control efforts.

While fresh MERS-CoV cases were reported from The Kingdom of Saudi Arabia, fears were growing that Hajj season may allow for a large scale spread of the virus. The publicized health education messages at that time called upon the most-at-risk group to postpone going to Hajj and Umrah, be assessed for medical fitness, get vaccinated against seasonal flu, and avoid the crowded and badly ventilated areas. This group involved elderly and patients with chronic illnesses or impaired immunity. Afterwards, frequent hand washing and drinking pasteurized camel milk or consuming well-cooked camel meat was advised along with minimizing close contact with symptomatic persons.

Discussion

The timeline of MERS-CoV events along with the communication activities in response to them gave a strong indication about the correlation between the media interest and public concern of a particular subject in hand, and the opportunities created by this momentum to communicate key information and recommended course of action by the competent authorities to satisfy the public's needs on the other hand.

Three main factors influenced how MERS-CoV was perceived in Qatar: its unfamiliarity, the epidemiological link to camels, and the way media had portrayed it. Like any other exotic risk, MERS-CoV's acknowledged unfamiliarity even to health officials seduced the media to fill the uncertainty vacuum by persistently focusing on the similarities with the deadly SARS epidemic that erupted in 2002, thereby allowing for scary scenarios to seed in the public's imagination. It was then announced that a kind of relationship had been established between the infected persons and camels before a Qatari scientific team declared that the life MERS CoV was isolated from an infected camel. The immediate result of this perceived risk was heightened public attention and interest. However, the repeatedly announced symptoms of suspected cases allowed for better identification and induced voluntary reporting of cases to healthcare facilities.

Substantial proportion of the communication process usually devoted to achieve the preparatory steps of seizing the audiences’ attention besides making sure that the content matters to them. Whereas the public need for information was being satisfied through news releases and press conferences, health education messages constituted a prime ingredient of the communication content.

Despite of the denial and stigma linked to the unfamiliar disease, the communicated health messages had a tangible influence on giving the target audience the information necessary to take decisions on the personal and community level. According to records of the medical Hajj committee, response to the pre-travel medical assessment and vaccination was remarkable. Patients complied with the isolation requirements. Nevertheless, Information, Education, and Communication (IEC) materials were not prepared prior to the press conferences, indicating missed opportunities.

After all, no significant rejection to the recommended course of action was identified.

Study limitations

As this study was based on reviewing the content of print media, other types of mass media were excluded. Moreover, it was important to determine the extent to which the target communities relied on official press releases and press conferences to gain information related to MERS-CoV.

Conclusion

Couple of factors contributed to the successful engaging of the target communities to adopt the recommended course of action: the perceived risk of the novel virus which made the public highly attentive, the timing of the health education messages that usually coincided with the critical disease developments, and the assignment of credible well-known resource officials from the competent authorities. As the public uptake of behaviors recommended by trusted authorities tends to be very high during epidemics, efforts should be made on designing health education messages to be injected within media products like press conferences and press releases during early preparedness phases.

Introduction

Urinary tract infection (UTI) is one of the most common pediatric infections. UTI may be associated with bacteremia and even meningitis in small babies, warranting full septic work up including a cerebrospinal fluid (CSF), especially in infants below the age of 60 days. Literature regarding the co-existence of meningitis in infants diagnosed with UTI is conflicting. It is critical to be able to correctly identify and treat any co-existing meningitis, as both the choice and duration of antibiotic used for UTI, is often insufficient to effectively treat meningitis.

Objective

The primary objective of this study was to determine the rate of co-existing bacterial meningitis in infants below the age of 60 days with a diagnosed urinary tract infection (UTI) and to determine if age, sex and prematurity and bacteremia were risk factors.

Method

A retrospective observational study was conducted at Hamad General Hospital, a tertiary medical institution in the State of Qatar. Patients under the age of 2 months hospitalized with a first episode of UTI from January 1, 2008 to December 31, 2013 were included in the study. UTI was defined as urine culture growing a single organism, with a colony count of greater than 103, where in the urine sample was obtained by either catheterization or supra-pubic aspiration. Infants with pre-exisiting clinical conditions like spina bifida or meningomyelocele and those diagnosed with congenital renal anamolies, were excluded from the study because of their higher likelihood of developing UTI. Infants with a questionable diagnosis of UTI (not in accordance with American Academy of Pediatrics definition of UTI) were also excluded.The study was approved by the Medical Research Center at Hamad Medical Corporation.

Results

113 patients met the inclusion criteria. 51 patients (44.3%) were neonates (0?28 days old) and 64 patients (55.7%) were between the age group of 29 to 60 days. 43.5% of the infants were male, and most (86.1%) were term. All 113 patients had culture proven UTI. The commonest pathogens causing UTI were Escherichia coli (38%), Klebsiella pneumoniae (15%), Enterococcus faecalis (13%), Group B Streptococcus sp(7%), and Citrobacter (6%). As per the routine practice in our institution, blood culture was ordered in all but one patient. Among these 112 patients, 3 (2.6%) had bacteremia. All 3 patients were Term female babies, 2 of them were neonates and 1 was between 29 to 60 days of age. Of the three pts who had a positive blood culture, CSF study was done in two babies, which was negative and 1 patient's family refused CSF study. A cerebrospinal tap was done in 78 patients i.e. 69% of the sudy population. None of these patients had a postive CSF culture. Physicians were more likely to order a CSF study in babies who were neonates (80% had a CSF study, as opposed to 60.3% of babies in the 29 to 60 day age group).

Conclusion

Our study demonstrated that in the 78 patients with culture proven UTI, who had a CSF study, none of the patients had co-existing bacterial meningitis. Our results are reflective of several other studies which also show a low risk of meningitis in patients with UTI. We tried to overcome some of the limitations of these studies by maintaining very strict criteria for diagnosing UTI. CSF study is a part of the septic work up in neonates. In contrast for patients between the age group of 29 to 60 days, more selective approach to lumbar puncture is warranted.

Background: Many health organizations are always highlighting the importance of health promotion, and disease prevention, due to the high incidence of chronic diseases that are spread worldwide and increasing continuously. One of the most prevalent chronic diseases is diabetes mellitus (DM). Many studies conducted in developed countries proved that lifestyle changes in patients resulted in a reduction in the prevalence of diabetes, and that there's a link between DM, and behavioral, clinical, and economical outcomes. Furthermore there was an affiliation between knowledge, attitude, and practice (KAP), and DM. Even though self-management of type 2 diabetes is necessary in order to improve quality of life, many patients still have a problem with being able to self-manage diabetes. Many models and interventions were tested to enhance self-management but none were successful so far. Self-management is a socio-behavioral problem, and the use of a model such as the transtheoretical model (TTM) could improve it. TTM is one of the most commonly used behavioral models. It was first introduced in the 1980s by Prochaska and DiClemente to explain how people change their behavior, but not why they change. It is a model of choice that focuses on the decision making capabilities of individuals. This model is different to alternative approaches to health promotion in that its primarily focus is not on social and biological behavioural influences. It is a psychological health promotion model about the intention of change. It is a model of choice that focuses on the decision making capabilities of individuals. It first uses the baseline information, with an aim to alter self-efficacy, cues, or other psychosocial factors using five TTM principles: Precontemplation, Contemplation, Preparation, Action, and Maintenance. Objective: The objective of this study is to collect enough evidence using a systematic review in order to assess the use of TTM in improving self-management activities in type 2 diabetic patients. Self-management activities include following a healthier diet, exercising more regularly, and an enhanced medication adherence. Methods: The systematic review was conducted between February and May 2015. PubMed (n = 83), Medline (n = 126), Science direct (n = 985), and Cochrane (n = 62) were the databases searched with predefined terms relating to TTM interventions for type 2 diabetic patients. A second extensive search was conducted using google, and google scholar (n = 2) to retrieve articles relevant to the research. The search strategy aimed to identify articles in which the Transtheoretical model had been applied and which had been published in English between 2000 and March 2015. In order to ensure that all potentially relevant articles had been identified, the search terms included “Transtheoretical model”, “Sociobehavioral”, “social changes”, “diabetes”, and “self-management”. All study designs were included and no limits were set to articles comparing the behavioral model to other approaches. The methods used for this review followed the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The systematic search was conducted in March 2015. The initial search of the above strategy yielded 1,153 articles. These articles were reviewed by the primary author for relevance to the aims of the review. Retained articles were then assessed for relevance to the aims based on the title and the abstract using the inclusion criteria. Articles identified as potential for inclusion were then retrieved. Each step during the selection process was conducted by two researchers, and in case of disagreement, consensus would be reached with the aid of a third researcher. Results: There was consensus in the review team that the 10 papers met the inclusion criteria. The 10 studies included were published between 2003 and 2011, and were conducted in the US (n = 6), Canada (n = 1), Trinidad and Tobago (n = 1), Scotland (n = 1), and one was unspecified. In all 10 studies, the majority of participants at baseline were at the Precontemplation/Contemplation or Preparation stage, and after the TTM intervention the majority of patients were at the Action or Maintenance stage. Four studies did not specify which stage had the highest number of participants at baseline and post TTM intervention. In one study, the highest number of participants was at the preparation stage (39.1%) at baseline, and after the TTM intervention the highest number of patients was in the action phase (45.7%) indicating an advancement through the stages of change. Moreover, in 4 studies most of the patients at baseline were in the pre-action stage, but at follow-up after the TTM interventions most of the participants moved to the action or maintenance stage. In one study, the greatest number of participants was at the action/maintenance stage pre- and post- the TTM intervention. All studies demonstrated some positive outcomes self-management due to implementing TTM. Four studies reported a significant reduction in glycosylated hemoglobin (HbA1c), 5 studies reported improvements in diet after TTM, and Participants exercised more in 2 studies. In one study there was progress towards reaching participants’ goals whether it's better adherence, diet, or more exercise. However, using the TTM had no change on medication use in any of the studies included. Moreover, Different study designs were used in all studies. 2 studies were pre-test/post-test. In addition, there were 3 Randomized controlled trials (1 was an RCT, 1 was a randomized split plot design where there was a group receiving the usual care and another receiving the intervention, and another study was a cohort randomized controlled prospective trial). One study was a quasi-experimental study. Three studies were reviews; one was a preliminary study which is an economic evaluation of a theoretical cohort of patients. The other one was a study describing how resources and supports for self-management (RSSM) and strategies of the transtheoretical model intersect to produce a comprehensive approach resulting in cutting-edge diabetes Program, and the last review was determining the impact of TTM in changing the unhealthy dietary habits of type 2 diabetic patients. Moreover, one article followed a cross sectional study design which consisted of questionnaires. Conclusion: Ten articles using TTM to self-manage type 2 diabetes were identified and critically reviewed. The narrative findings from this systematic review provide evidence that TTM interventions are effective in promoting exercise, and encouraging participants to pursue a healthier diet. However, the effect of TTM on medication adherence has not been clearly identified yet, and it should be studied in future research.

Introduction: Doha city has a high feral cat population that is estimated to outnumber its human inhabitants by 2-3:1 with a total population of 2-3 million cats according to Qatar Cat Control Unit (QCCU). Doha had a significant rodent problem for decades as in many cities throughout the world. It was difficult to control this huge rodent number. Therefore, cats were introduced in the 1960s, but without any consideration of the possible knock-on effects to human health. Introduced cats have colonized and reproduce rapidly around food and water resources in both urban and rural areas. It is known that cats are natural host for a wide range of helminths and protozoa. Since there were no plans to eliminate cats after they have been introduced to the country, the density of cats increased in an uncontrollable manner. This high cat population has an obvious risk for human and different diseases such as toxoplasmosis would be expected. Hospital records show that human toxoplasmosis is quite widespread in the city, with up to 35% of women of childbearing age being reported to be seropositive, and 41% of the elderly persons of both sexes in the population. These findings highlight the role cats might be playing in the transmission of protozoa in the society. Cats are also hosts to other closely related species of intestinal protozoa. For example, cats can harbour Isospora spp., Cryptosporidum felis, Giardia intestinalis and Blastocystis spp. Given the high density of cats in the city, it is clearly important to assess the prevalence of protozoal infections among these animals as a first step towards achieving a better understanding of their role in the transmission of human infectious disease of feline origin eventually. Objectives: Since Doha has a high feral cat population, there is a need to understand the role of cats as vectors of human protozoal infections. Our preliminary data indicate that Blastocystis spp. and Toxoplasma gondii is highly prevalent among the residents of Doha. In this project, it was proposed to estimate the prevalence of gastrointestinal protozoa including Giardia intestinalis, Cryptosporedium parvum and Blastocystis hominis in the feral cat population in Doha. A total of 264 fecal samples will be collected from feral cat population from different geographical locations of Doha. Advanced technologies will be used including DNA extraction, RT-PCR and sequencing to provide an accurate assessment of the prevalence. Methodology Study area and Population: Fresh stool samples were collected from cats in different areas in Qatar. In this study, 37 areas were divided into two geographical regions: outside Doha and inside Doha based on occupation of people. Cats were trapped during the winter (November–April) and the summer (May–October) seasons of 2015. Traps were prepared with fish heads or canned cat food. Cats were retrieved from traps and assessed for sterilization status. Pregnant, lactating female cats and cats estimated to be less than 6 months old were immediately released. Cats older than 6 months were eligible for the study. In order to prevent any repetition and re-sampling of cats already and treated earlier, cat's ear will be tagged with a small metal tag. All project ethical approvals were obtained before the beginning of the project. Samples Collection Fresh stool samples were collected from sterilized cats during the period from February–September 2015 and stored at -20 °C by veterinary laboratory of stray cat control unit in Ministry of environment (department of animal resources). A total of 264 samples were processed in order to achieve the aim of this project. Samples were collected in sterile containers labeled with site, where the cat is found, gender and date of collection. The samples were kept and transported on ice and frozen directly after the sample collected. Fecal Examination In order to extract the DNA of the enteric pathogens samples were warmed at 4 °C and approximately 200 mg of the stool sample were used for examination. QIagen miniamp stool kit was used to extract DNA from the sample following manufacturer's instructions with minor modifications. Lyses buffer ASL was added and mixed with each stool sample. Since cat stool is hard to break, tissue rupture machine was used to ensure the homogenization of the sample and increase DNA recovery. This is followed by vortexing the samples and incubating them at 95 °C for 10 minutes to insure complete lysis. After lysis, samples were centrifuged for 10 minutes at 4500 rpm in order to separate and pellet the stool particles. After that, supernatant were placed in new microcentrifuge tubes. Using InhibitEx binding reagent DNA-degrading substances and PCR-inhibitors were separated and removed from the sample. The DNA InhibitEx matrix was centrifugated twice at 14,000 rpm for 3 minutes to pellet the stool and any impurities. 15 μL of proteinase K, 200 μL of the supernatant and 200 μL of the buffer AL were all added to new microcentrifuge and incubated at 70 °C for 10 minutes. Proteinase K is used to digest protein and remove contamination and inactivates nucleases which degrade the DNA during the purification process. However, in order to make proteinase K work high temperature is needed to denature proteins. Therefore, samples are incubated at 70 °C for 10 minutes. Supernatant part containing DNA was then transferred to a Qiagen Minispin column. Two different washing buffers with optimized pH and salt concentration were added to eliminate the digested proteins and any other impurities. Samples were centrifuged at 14,000 rpm before the addition of each buffer. Finally using AE buffer the DNA was eluted. DNA concentration was measured using Nanodrop (Thermo Fisher Scientific, USA). Primers and Probes Using primer designing software, the primer and probe sets used for detecting parasitic pathogens were designed based on data available in National Center for Biotechnology Information (NCBI) databases. Targeted genes were chosen based on published data and studies describing their sequences, uniqueness, and conservation. Real-time PCR Samples were analyzed by uniplex real-time PCR using Applied Biosystems Cycler 7500. Protocols were finalized after adjustment of the respective concentrations of primers, probes and the evaluation of several cycling protocols. A proposed protocol based on available literature was a starting point. Two different fluorescence reporter dyes were used in Real-time PCR. SYBR Green was used for Blastocystis hominis and TaqMan for other targeted parasites. For both fluorescence reporter dyes amplification reactions were performed in a total 20 μL volume in each well with 17.5 μL master mix and 2.5 μL DNA template. For each plate prepared positive controls consisted of internal controls provided by Hamad Medical Corporation (HMC). Both positive and negative controls were run for each sample. Sample PCR results were compared with both controls and analyzed using 7500 software v2.3. Results: A total of 264 of stray cat samples were trapped for examination of enteric parasite. The samples were classified according to their gender, area and season. Table (1) summarized the frequency of the cat population examined. Three protozoal parasites (Giardia intestinalis, Cryptosporidium parvum and Blastocystis hominis) were examined using real-time PCR. According to PCR results obtained previously, Giardia intestinalis was the only protozoa positively detected. Table (2) shows the prevalence of examined protozoa in cat samples. Figure 1 and Fig. 2 show the interaction between Giardia intestinalis infection and other independent variables (gender, season and area). Table 1. Number of stray cats examined by season, gender and study site from Qatar during 2015 Season Winter Summer Male Female Male Female Site N N N N Outside Doha 44 (16.67%) 39 (14.77%) 25 (9.47%) 23 (8.71%) Inside Doha 34 (12.88%) 20 (7.58%) 37 (14.01%) 42 (15.91%) Total 78 59 62 65 *N, number of samples; the number in brackets indicates the percentage of prevalence. Table 2. Number of subjects in each category and the prevalence (%) of the three species of protozoa by gender, season and area Number of subjects Giardia intestinalis Cryptosporidium parvum Blastocystis hominis Gender Male 140 5 0 0 Female 124 7.2 0 0 P 0.443 (NS) NS NS Season Winter 137 6.5 0 0 Summer 127 5.5 0 0 P 0.719 (NS) NS NS Area Outside Doha 131 5.34 0 0 Inside Doha 133 6.77 0 0 P 0.628 (NS) NS NS *NS: not significant **The highest prevalence in each category is in bold italics for emphasis. Benefits to Qatar This study will provide important data for the public healthcare, which they can exploit to determine the role feral cat might be playing in zoonotic diseases in Doha. The training in research methodologies will also foster the interest in research the undergraduate students have and therefore add to the pool of qualified researchers in Qatar.