Therapeutic management of Urinary Tract Infections (UTI): A retrospective study in two Teaching Hospitals in Nigeria

Urinary Tract Infection (UTI) is one of the most common diseases and a significant cause of morbidity in all age groups. There are large differences in the management of UTI with respect to definition, diagnosis and treatment. This retrospective study reviewed the diagnosis and drug treatment of UTI at the Teaching Hospitals of Ahmadu Bello University (ABUTH), Zaria and University of Maiduguri (UMTH). The results showed that majority of the infectionswere due to Escherichia coli, followed by Klebsiella species and Staphylococcus aureus. The symptoms were dysuria, suprapubic pain, fever and/or chills, and lower abdominal discomfort, which differed in order of occurrence at the two institutions. The infecting organisms were sensitive to pefloxacin, ceftriazone and gentamicin while the most frequently used antibiotics were gentamicin, ciprofloxacin and ampicillin/cloxacillin in decreasing order at ABUTH. At UMTH,ceftazidine, ofloxacin and gentamicin were frequently active against the infective organisms; and the most prescribed antibiotics were nitrofurantoin, ofloxacin, amoxicillin/clavulanic acid and co-trimoxazole in decreasing order. These results showed that institutional antibiotic policy in the treatment of urinary tract infections might have been based on the experience of the physician, cost of the drug and route of administration instead of prevalence and sensitivity patterns. It also showed that the guiding principle of the rational use of drugs is not strictly adhered to

Lifestyle, environmental and occupational factors associated with follicular lymphoma risk and survival in Australia

Follicular lymphoma (FL) accounts for one-third of incident non-Hodgkin lymphomas in Western countries, but its etiology is largely unexplained. I performed systematic reviews and meta-analyses, and used a population-based family case-control study to investigate the relationship between lifestyle, environmental and occupational risk factors of FL. Meta-estimates from my random-effect models showed a non-significant association with smoking, heterogeneous results for alcohol, modest increased risk with obesity, and positive associations with exposure to polychlorinated biphenyls (PCBs), chlorinated solvents and dichlorodiphenyldichloroethylene (DDT, a pesticide). The population-based case-control study included 770 FL cases and 490 family controls (siblings, partners). Participants completed a lifetime residential and work calendar and health, lifestyle, and diet questionnaires. I used unconditional logistic regression to examine associations with FL risk, including group-based trajectory modeling to examine associations with body shape and outdoor hours over the life course. I identified deaths using record linkage and applied Cox proportional regression to estimate hazard ratios for all-cause and FL-specific mortality. I observed a positive association between smoking and FL risk and mortality. Associations with recent alcohol intake and FL were null. Being obese 5 years prior to enrolment and higher body mass index 5 years prior to enrolment was associated with a modest increased FL risk, but there was no association with body shape trajectory. Body size was not associated with mortality. I observed an elevated FL risk with consumption of oily fish, but no association with mortality. I found no significant association between occupational exposure to pesticides, or extremely-low frequency magnetic fields, and FL risk. For sun exposure, I observed an inverse association with high cumulative outdoor hours and high outdoor hour maintainers over the life course, and FL risk. Policies on tobacco control, maintaining body weight within normal range, and safe use of solvents and pesticides are crucial in reducing the burden from FL. Sun exposure is not recommended as a cancer control policy, but the association may inform research on targeted therapies for this malignancy. My key findings have advanced our understanding of FL etiology and help guide risk reduction strategies and future research

Exploring the Integration of Corporate Sustainability Into Small-Scale Business Activities

Small and medium-scale enterprises contribute 49% of the gross domestic product in Nigeria. The lack of research studies on how small and medium-scale enterprises integrate corporate sustainability into their business operations might present challenges for policymakers in achieving Nigeria’s sustainable development goals (SDG). The purpose of this descriptive phenomenological study was to explore how managers of small and medium-scale enterprises integrate the corporate sustainability dimensions into their business operations based on the concepts of the corporate entity, corporate nature, and corporate obligations. The central research question of this study was how managers of small and medium-scale enterprises integrate the economic, social, and environmental sustainability dimensions. Data were collected through online interviews of 12 managers with a minimum of relevant sustainability management experience using purposive sampling strategies. Interviews were transcribed and analyzed through Giorgi’s phenomenological method. Significant findings showed that managers integrate sustainability through sustainable supply chain practices, regulatory compliance, organizational culture change, inclusive governance, and innovation. The results could contribute to positive social change by enhancing policies towards achieving SDGs in developing countries like Nigeria

Molecular characterization of the tetratricopeptide repeat-mediated interactions of murine stress-inducible protein 1 with major heat shock proteins

Murine stress-inducible protein 1 (mSTI1) is a co-chaperone that is homologous with the human heat shock protein 70 (Hsp70)/heat shock protein 90 (Hsp90)-organizing protein (Hop). The two proteins are homologues of the highly conserved stress-inducible protein 1 (STI1) family of co-chaperones. The STI1 proteins interact directly and simultaneously at some stage, with Hsp70 and Hsp90 in the formation of the hetero-multi-chaperone complexes that facilitate the folding of signal transducing kinases and functional maturation of steroid hormone receptors. The interactions of mSTI1 with both Hsp70 and Hsp90 is mediated by a versatile structural protein-protein interaction motif, the tetratricopeptide repeat (TPR). The TPR motif is a degenerate 34-amino acid sequence a-helical structural motif found in a significant number of functionally unrelated proteins. This study was aimed at characterizing the structural and functional determinants in the TPR domains of mSTI1 responsible for binding to and discriminating between Hsp70 and Hsp90. Guided by data from Hop's crystal structures and amino acid sequence alignment analyses, various biochemical techniques were used to both qualitatively and quantitatively characterize the contacts necessary for the N-terminal TPR domain (TPR1) of mSTI1 to bind to the C-terminal EEVD motif of heat shock cognate protein 70 (Hsc70) and to discriminate between Hsc70 and Hsp90. Substitutions in the first TPR motif of Lys⁸ or Asn¹² did not affect binding of mSTI1 to Hsc70, while double substitution of these residues abrogated binding. A substitution in the second TPR motif of Asn⁴³ lowered but did not abrogate binding. Similarly, a deletion in the second TPR motif coupled with a substitution of Lys⁸ or Asn¹² reduced but did not abrogate binding. Steady state fluorescence and circular dichroism spectroscopies revealed that the double substitution of Lys⁸ and Asn¹² resulted in perturbations of inter-domain interactions in mSTl1. Together these results suggest that mSTI1-Hsc70 interaction requires a network of electrostatic interactions not only between charged residues in the TPR1 domain of mSTI1 and the EEVD motif of Hsc70, but also outside the TPR1 domain. It is proposed that the electrostatic interactions in the first TPR motif collectively made by Lys⁸ and Asn¹² define part of the minimum interactions required for successful mSTI1-Hsc70 interaction. In the first central TPR domain (TPR1A), single substitution of Lys³°¹ was sufficient to abrogate the mSTI1-Hsp90 interaction. Using a truncated derivative of mSTI1 incapable of binding to Hsp90, residues predicted by crystallographic data to determine Hsp70 binding specificity were substituted in the TPR1 domain. The modified protein had reduced binding to Hsc70, but showed significant binding capacity for Hsp90. In contrast, topologically equivalent substitutions on a truncated derivative of mSTI1 incapable of binding to Hsc70 did not confer Hsc70 specificity on the TPR2A domain. These data suggest that binding of Hsc70 to the TPR1 domain is more specific than binding of Hsp90 to the TPR2A domain. In addition, residues C-terminal of helix A in the second TPR motif of mSTI1 were shown to be important in determining specific binding to Hsc70. Binding assays using surface plasmon resonance spectroscopy showed that the affinities of binding of mSTI1 to Hsc70 and Hsp90 were 2 μM and 1.5 μM respectively. Preliminary in vivo studies revealed differences in the dynamics of binding of endogenous and exogenous recombinant mSTI1 with Hsc70 and Hsp90. The outcome of this study poses serious implications for the mechanisms of mSTI1 interactions with Hsc70 and Hsp90 in the cell

Pregnancy and contraceptive use among women participating in an HIV prevention trial in Tanzania.

OBJECTIVES: Information on pregnancy rates and factors associated with pregnancy and contraceptive use is important for clinical trials in women in sub-Saharan Africa where withdrawal of investigational products may be required in the event of pregnancy with a consequent effect on sample size and trial power. METHODS: A prospective cohort analysis of pregnancy and contraceptive use was conducted in Tanzanian women enrolled in a randomised placebo-controlled trial of herpes simplex virus-suppressive therapy with acyclovir to measure the effect on HIV incidence in HIV-negative women and on genital and plasma HIV viral load in HIV-positive women. The cohort was followed every 3 months for 12-30 months. Women at each visit were categorised into users or non-users of contraception. Pregnancy rates and factors associated with pregnancy incidence and contraceptive use were measured. RESULTS: Overall 254 of 1305 enrolled women became pregnant at least once during follow-up (pregnancy rate: 12.0/100 person-years). Younger age, being unmarried, higher baseline parity and changes in contraceptive method during follow-up were independently associated with pregnancy. Having paid sex and being HIV positive were associated with lower risk of pregnancy. Uptake of contraception was associated with young age, being unmarried, occupation, parity and the number and type of sexual partners. CONCLUSIONS: Data on use of contraceptive methods and risk factors for pregnancy can help to guide decisions on trial eligibility and the need for additional counselling. Mandatory reliable contraceptive use in study participants may be required to reduce pregnancy rates in studies where pregnancy is contraindicated

Fruits and Vegetables Diet Improves Kidney Functions and Electrolyte Status in Non-Insulin Dependent Diabetes Mellitus (N.I.D.D.M) Subjects

Kidney failure and electrolyte imbalance are some of the complications associated with diabetes mellitus, if prompt treatment is not instituted it may lead to renal disease and dietary influence has been established on the prognosis of many diseases. Thus effects of fruits and vegetables diet were investigated on kidney functions and electrolyte status of some selected Non-Insulin dependent diabetic subjects at the cardiovascular clinic of Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria. The patients with mean fasting blood glucose (FBG) 7.84± 0.95 mmol dl-1 were placed on 300 g of fruits and vegetables per day in addition to their normal drugs and food intake for eight weeks. Standard laboratory methods were employed for biochemical assay; while the data were analyzed using analytic and descriptive statistics. A significant difference (p < 0.05) was noticed between baseline and eighth week’s values in the following parameters: plasma creatinine, 3.48± 0.095 to 1.79±0.57 mgdL-1; urea, 39.05±2.04-23.20±1.50 and uric acid 5.37± 0.27-2.50±0.59 mgdL-1. No significant difference (p > 0.05) was observed in plasma electrolyte values when the    baseline value were compared with the eighth week’s values. After the eight weeks, the fruits and vegetables rations were stopped for two weeks and the parameters were measured again. Significant difference(p<0.05) were observed in all the values by comparing week eight with week ten values; plasma creatinine, 1.79±0.52 to 3.01± 0.68 mgdl-1,plasma urea, 39.05± 2.40 to 23.20± 1.50  mgdl-1 and plasma uric acid 2.50±0.59 to 3.61±0.50 mgd-1, however no significant difference (p> 0.05) was observed in serum electrolyte. Our results showed that fruits and vegetables consumption improved kidney function and did not affect plasma electrolytes adversely. KEY WORDS: Diabetes mellitus, kidney functions, creatinine, urea, uric acid fruits and vegetable

Epidemiology of Staphylococcus aureus carriage and disease among under five children in rural Gambia

Background: Data on the burden of severe Staphylococcus aureus disease, a significant cause of invasive bacterial infections among children aged <5 years in The Gambia and Africa at large, are lacking. The work in this thesis estimates the burden (cases and deaths) of severe S. aureus disease in Africa, the incidence of S. aureus bacteraemia (SAB) in children aged <5 years and assesses the risk factors for neonatal S. aureus acquisition in rural Gambia. Methods: This thesis includes three separate studies. First, following a systematic literature review and meta-analysis, raw and processed data were synthesised to estimate the numbers of cases and deaths due to severe S. aureus diseases in children aged <5 years in Africa. Second, the incidence and case fatality ratio (CFR) of SAB in <5 years Gambian children were estimated from a population-based study. Lastly, a longitudinal study of newborn-contact pairs was used to evaluate the risk factors associated with neonatal S. aureus carriage at birth as well as with its acquisition at one-week of age. Results: In Africa, an estimated 392,066 cases and 46,467 deaths due to severe S. aureus disease occurred among children aged <5 years with 20.4% and 58.4% of these occurring among neonates, respectively in 2015. The incidence of SAB among Gambian children aged <5 years and neonates was 78/100,000 person-years (95%CI 67–91) and 3.5/1,000 live-births (95%CI 2.9–4.7), respectively. The CFR was 14.1% (95%CI 9.6-19.8). S. aureus carriage at birth was associated with the midwife’s report of handwashing before delivery while carriage acquisition one week after delivery was associated with maternal and household child nasal carriage. Conclusion: The burden of severe S. aureus disease among children aged <5 years in Africa is substantial. Developing new, and implementing existing, strategies urgently to tackle this will contribute to achieving the sustainable development goals

Conducting defect with atrial septal aneurysm in a preterm neonate: A case report from resource limited setting

Conducting defect (CD) co-existing with interatrial septal anomaly (ISA) like Atrial Septal Aneurysm (ASA) is a rare congenital heart disease presenting with bradyarrhythmia in-utero due to defects in the heart electrical conducting system. We report a case of a preterm female ‘CC’ (GA=35weeks) low birth weight (2.4kg) neonate with CD and associated ASA. CC’s mother presented with poor foetal movements and bradyarrhythmia and had an emergency caesarian section at 35weeks with Apgar score of 3, 5. She was managed for perinatal Asphyxia. This report highlights the fact that ASA resolved at around the first year of life but the associated heart electrical conducting system defects persisted. The report also emphasizes the challenges of managing a rare neonatal cardiac condition in a resource limited setting and the importance of thorough foetal biophysical profile and early interventional delivery when it is necessary.Keywords: Conducting defect; neonatal; Atrial Septal Aneurysm

Hybridized centroid technique for 3D Molodensky-Badekas coordinate transformation in the Ghana geodetic reference network using total least squares approach

The Molodensky-Badekas model is one of the similarity transformation models used in Ghana for transferring Global Positioning System (GPS) coordinates from the geocentric World Geodetic System 1984 (WGS 84) ellipsoid to the local non-geocentric coordinate system, and vice versa. The objective of the Molodensky-Badekas model is to introduce a centroid to cater for the correlation that exists between the parameters when used over a small portion on the earth surface. However, the Molodensky-Badekas model performance depends on a particular centroid method adopted and the adjustment technique used. By virtue of literature covered, it was realised that the arithmetic mean centroid has been the most widely used. In view of this, the present study developed and tested two new hybrid centroid techniques known as the harmonic-quadratic mean and arithmetic-quadratic mean centroids. The proposed hybrid approaches were compared with the geometric mean, harmonic mean, median, quadratic mean and arithmetic mean. In addition, the Total Least Squares (TLS) technique was used to compute the transformation parameters with varying centroid techniques to investigate and assess their accuracies in precise GPS datum transformation parameters estimation within the Ghana Geodetic Reference Network. Statistical indicators such as Mean Error (ME), Mean Squared Error (MSE), Standard Deviation (SD), and Mean Horizontal Position Error (MHPE) were used to assess the centroid techniques performance. The results attained show that the Harmonic-Quadratic Mean produced reliable coordinate transformation results within the Ghana geodetic reference network and thus could serve as practical alternative technique to the frequently used arithmetic mean.Keywords: Coordinate transformation, Molodensky-Badekas model, Centroid, Total Least Square