Domains required for the interaction of the central negative element FRQ with its transcriptional activator WCC within the core circadian clock of Neurospora.

In the negative feedback loop composing the Neurospora circadian clock, the core element, FREQUENCY (FRQ), binds with FRQ-interacting RNA helicase (FRH) and casein kinase 1 to form the FRQ-FRH complex (FFC) which represses its own expression by interacting with and promoting phosphorylation of its transcriptional activators White Collar-1 (WC-1) and WC-2 (together forming the White Collar complex, WCC). Physical interaction between FFC and WCC is a prerequisite for the repressive phosphorylations, and although the motif on WCC needed for this interaction is known, the reciprocal recognition motif(s) on FRQ remains poorly defined. To address this, we assessed FFC-WCC in a series of frq segmental-deletion mutants, confirming that multiple dispersed regions on FRQ are necessary for its interaction with WCC. Biochemical analysis shows that interaction between FFC and WCC but not within FFC or WCC can be disrupted by high salt, suggesting that electrostatic forces drive the association of the two complexes. As a basic sequence on WC-1 was previously identified as a key motif for WCC-FFC assembly, our mutagenetic analysis targeted negatively charged residues of FRQ, leading to identification of three Asp/Glu clusters in FRQ that are indispensable for FFC-WCC formation. Surprisingly, in several frq Asp/Glu-to-Ala mutants that vastly diminish FFC-WCC interaction, the core clock still oscillates robustly with an essentially wildtype period, indicating that the interaction between the positive and negative elements in the feedback loop is required for the operation of the circadian clock but is not a determinant of the period length.

Site matters: Image-guided percutaneous sampling of intervertebral disc results in increased positive diagnostic yield in spondylodiscitis.

Spondylodiscitis is a common referral to spinal on call services. Identification of the causative organism is vital in order to dictate the appropriate antibiotic treatment. In this context, the surgical and interventional radiology team is often asked to perform a diagnostic biopsy. The aim of the present study was to assess whether the sampling location affects the diagnostic yield. Our results suggest that the overall positive diagnostic yield was 35%. When disc material was included in the sample the diagnostic yield significantly improved to 47%. Bone sampling alone had a positive yield of 15%. Age, pre-biopsy CRP, pre-biopsy use of antibiotics did not seem to affect the likelihood of obtaining a positive yield. These results suggests that when performing image guided biopsies for suspected cases of spondylodiscitis the inclusion of disc material is important.

Patients' and primary carers' views on clozapine treatment for schizophrenia: A cross-sectional study in Qatar.

Subjective views of clozapine treatment among patients with schizophrenia in the Middle East and North African MENA Region have not previously been assessed. Globally, few studies have assessed the views of carers to clozapine treatment. We conducted a cross-sectional survey, using a clinician administered structured interview, of patients with schizophrenia/schizoaffective disorder prescribed clozapine in Qatar, and their primary carers. Participants were asked to rate clozapine against prior their antipsychotic treatment in terms of specific benefits and side effects. Forty-two patients and 33 carers participated in the study. Of the patients, two thirds were male, approximately half were Qatari and the mean age was 33.9 years. Patients and carers rated clozapine as superior to prior antipsychotic treatment on all 7 potential benefits inquired about. The greatest perceived benefit was improved mood. Patients rated clozapine as less likely to cause extrapyramidal side effects but more likely to cause 18 other potential side effects compared to prior antipsychotic treatment, with the greatest difference being for nocturnal salivation, increased appetite, and constipation. Nearly half of patients (48 %) and two thirds of carers (64 %) stated that they would have preferred to start clozapine earlier in their illness. Sixty percent of patients and 37 % of carers regarded the information that they had received from health professionals on clozapine as inadequate. Less than half of patients and approximately-two thirds of carers had adequate knowledge of haematological monitoring for clozapine. Generally, there were significantly positive correlation between patients and carers regarding the overall side effects of clozapine treatment. Likewise, improvement in hearing voices paranoid thoughts correlated with improved quality of life. In summary, the results show that patients and carers appreciate the benefits of clozapine despite its side effects being problematic. The results support clozapine being offered earlier in treatment and services providing more information on clozapine to patients and carers.

World competitive contest-based artificial neural network: A new class-specific method for classification of clinical and biological datasets.

Many data mining methods have been proposed to generate computer-aided diagnostic systems, which may determine diseases in their early stages by categorizing the data into some proper classes. Considering the importance of the existence of a suitable classifier, the present study aims to introduce an efficient approach based on the World Competitive Contests (WCC) algorithm as well as a multi-layer perceptron artificial neural network (ANN). Unlike the previously introduced methods, which each has developed a universal model for all different kinds of data classes, our proposed approach generates a single specific model for each individual class of data. The experimental results show that the proposed method (ANNWCC), which can be applied to both the balanced and unbalanced datasets, yields more than 76% (without applying feature selection methods) and 90% (with applying feature selection methods) of the average five-fold cross-validation accuracy on the 13 clinical and biological datasets. The findings also indicate that under different conditions, our proposed method can produce better results in comparison to some state-of-art meta-heuristic algorithms and methods in terms of various statistical and classification measurements. To classify the clinical and biological data, a multi-layer ANN and the WCC algorithm were combined. It was shown that developing a specific model for each individual class of data may yield better results compared with creating a universal model for all of the existing data classes. Besides, some efficient algorithms proved to be essential to generate acceptable biological results, and the methods' performance was found to be enhanced by fuzzifying or normalizing the biological data.

Diagnostic value of post-operative platelet-to-white blood cell ratio after splenectomy in patients with advanced ovarian cancer.

INTRODUCTION: Splenectomy-induced thrombocytosis and leukocytosis may obscure the early diagnosis of post-operative infection or sepsis. In trauma patients after splenectomy, a platelet-to-white blood cell ratio of <20 has been shown to reliably differentiate post-operative sepsis from transient physiological responses. OBJECTIVE: To determine whether the platelet-to-white blood cell ratio can be applied to differentiate between reactive post-operative changes and latent infection. METHODS: All consecutive patients with ovarian cancer who underwent splenectomy between January 2013 and October 2018 in two large European gynecological cancer centers were retrospectively evaluated. Main outcome measures were white blood cell count, platelet count, and platelet-to-white blood cell ratio on post-operative days 1, 5, and 7. These were correlated with surgical outcome and morbidity according to the Clavien-Dindo classification. A binomial logistic regression was applied to assess the predictive value of day 5 platelet-to-white blood cell ratio, white blood cell count, and platelet count for predicting grade III post-operative sepsis. RESULTS: Ninety-five patients with ovarian cancer (mean age 54 years, range 18-75) were identified. Seventeen patients (17.9%) developed a grade III post-operative sepsis. In all post-operative patients, mean white blood cell count on day 5 decreased (from 15.4×103/µL to 11.4×103/µL), while the mean platelet count rose (from 260.7×103/µL to 385.3×103/µL). A high platelet count (>313×103/µL) failed to show any predictive value (OR=0.94; 95% CI 0.30 to 3.0; p=0.921). A low platelet-to-white blood cell ratio (<26) (OR=3.49; 95% CI 1.18 to 10.32; p=0.0241) and high white blood cell count (>14.5×103/µL) on day 5 (OR=11.0; 95% CI 3.3 to 36.2; p<0.001) were significant for predicting sepsis. Despite a significant OR, the sensitivity and specificity were low; day 5 platelet-to-white blood cell ratio at a cut-off point of 26 achieved a sensitivity of 72% and specificity of 53% (area under the curve 0.637, 95% CI 0.480 to 0.796) in predicting grade III post-operative sepsis. CONCLUSIONS: Platelet-to-white blood cell ratio after cytoreductive surgery for ovarian cancer with splenectomy does not appear to have a strong predictive value in differentiating between sepsis and reactive splenectomy-induced changes. Leukocytosis, in combination with clinical assessment, may remain the most useful tool for prediction of sepsis after cytoreductive surgery with splenectomy.

C-reactive protein has a better discriminative power than white cell count in the diagnosis of acute cholecystitis.

BACKGROUND: The diagnosis of acute cholecystitis (AC) is challenging and may result in a delay in surgery, hospital discharge, and increased mortality. To improve its diagnosis, C-reactive protein (CRP) has been proposed as a benchmark. The aim of this study was to evaluate discriminative power of CRP against white cell count (WCC) in AC. METHODS: This was a retrospective cohort study. Over a 5-y period, 1959 patients were identified from the audit of cholecystectomies. The exclusion criteria were coexisting acute surgical conditions, absence of blood tests within 3 d before hospital admission for elective surgery, and private patients. RESULTS: The eligibility criteria were met by 1843 patients. Comparison of the area under receiver operating characteristic (AUC) curve of CRP and WCC in acute on chronic, edematous, necrotic, suppurative, and gangrenous AC showed a better discriminative power of CRP. Both tests performed equally well in patients with pericholecystic abscess and gallbladder perforation. CRP was superior than WCC in mild AC, AUC = 0.93 (95% confidence interval [CI], 0.9-0.95) and 0.79 (95% CI, 0.74-0.84), P < 0.00005, in moderate and severe AC, AUC = 0.99 (95% CI, 0.97-1.0) and 0.92 (95% CI, 0.88-0.97), P = 0.009, and in all forms of AC combined, AUC = 0.94; (95% CI, 0.92-0.97) and 0.83 (95% CI, 0.79-0.87), respectively, P < 0.00005. CONCLUSIONS: CRP has a better discriminative power than WCC in most forms of AC and is a useful diagnostic marker of AC.

Personal health record use and association with immunizations and well-child care visits recommendations.

OBJECTIVE: To determine the association of parental use of integrated personal health records (PHRs) with children's adherence to immunization and well-child care (WCC) visit recommendations. STUDY DESIGN: For the immunization and WCC visit measures, we retrospectively analyzed, respectively, 766 and 639 matched pairs at Kaiser Permanente (KP) Hawaii and 2795 and 2448 pairs at KP Northwest who were ≤ 31 days old at enrollment and continuously enrolled for 2 years between January 2007 and July 2011. The independent variable (≥ 1 PHR feature used vs none) was matched using propensity scores on parental and children characteristics. The dependent variables were 2 measures from the 2010 Healthcare Effectiveness Data and Information Set: combination 2 immunization (all immunizations vs .05; KP Northwest OR 1.2, 95% CI 1.0-1.3, P < .05). PHR use was associated with better adherence to WCC visit recommendations for both KP Hawaii (OR 1.9, 95% CI 1.3-2.9, P < .001) and KP Northwest (OR 2.5, 95% CI 2.1-2.9, P < .001). CONCLUSIONS: Young children whose parents used a PHR were more likely to adhere to the recommended WCC visits in both regions but immunizations in only 1 region.

Genome resequencing and transcriptome analysis reveal the molecular mechanism of albinism in Cordyceps militaris.

Light is an important regulator of most fungal life activities and transmits signals through certain photoreceptor proteins such as phytochromes and cryptochromes. However, the light response mechanism varies across different fungi. The WCC complex composed of white collar-1 (WC-1) and white collar-2 (WC-2) is considered to be the key factor regulating fungal albinism. The photoreceptor protein Vivid (VVD) is the negative regulator of the WCC complex. In this study, we discovered an albino mutant (Alb) generated by 60Co-γ-ray irradiation from Cordyceps militaris (C. militaris). This mutant showed albinism of the mycelia and fruiting bodies under light, and the fruiting bodies developed normally. However, this phenotype in Alb differed from that in the CmWC-1 mutant. This suggests that CmWC1 may not be mutated in Alb. A mutated polyketide synthase (CmPKS) was found through genome resequencing analysis. CmPKS was significantly induced by a light signal, and its mutation reduced melanin accumulation in C. militaris. In addition, we found that a zinc-finger domain-containing protein (CmWC-3) was induced by a light signal and interacted with CmWC-1 and CmVVD. Moreover, CmWC-2 also interacted with CmWC-1 to form the WCC complex and was inhibited by CmVVD. In addition, CmWC-3 directly bound with the CmPKS promoter, but CmWC1 did not. These results suggest that albinism and fruiting body development are two independent processes; the WCC complex of CmWC-1 with CmWC-3 regulates CmPKS expression to regulate color change, whereas CmWC-1 with CmWC-2 affects fruiting body development via the carotenoid pathway. These findings will help us to better understand the albinism mechanism of C. militaris.

Evaluation of woman-centred care status by Iranian midwives and providing strategies to improve women-centred care: A sequential explanatory mixed method study protocol.

AIM: The present study aimed to evaluate the status of WCC provided by Iranian midwives. DESIGN: A sequential explanatory mixed method study protocol. METHODS: The present study was conducted in three phases: quantitative, qualitative and mixed. The first phase is a cross-sectional study that will be performed on midwives working in health centres, public and private hospitals in Iranian. The second phase is a qualitative study, in which purposeful sampling will be used, meaning that the midwives who are part of the extreme cases according to the results of quantitative phase and are willing and able to express their own experiences regarding WCC will be selected. Also, pregnant and parturient women under their cover will also be interviewed. Finally, in the mixed phase, we will use a combination of two quantitative and qualitative studies, a literature review and expert opinion using a Delphi method to provide strategies to improve and promote WCC in midwives. RESULTS: Achieving this goal is expected to provide positive outcomes such as strengthening the midwives professional relationship with women and reducing health care costs. No Patient or Public Contribution.

WBC Count vs. CRP Level in Laboratory Markers and USG vs. CT Abdomen in Imaging Modalities: A Retrospective Study in the United Arab Emirates to Determine Which Are the Better Diagnostic Tools for Acute Appendicitis.

Introduction Acute Appendicitis (AA) is the most common surgical emergency. Despite the use of various diagnostic parameters, the rate of negative appendectomy remains high (30%). Thus, through our retrospective study, we aim to analyse whether white blood cell (WBC) count or C-reactive protein (CRP) level is more indicative in the confirmation of AA. We also analysed imaging modalities ultrasonography (USG) and computed tomography (CT) of the abdomen to find out which is better for diagnosing AA. Methods Patients with suspected AA admitted for laparoscopic appendectomy in Saqr Hospital, Ras Al Khaimah, United Arab Emirates, during 2019-2020 were included in the study. Patients who had either or both WBC and CRP values were included in the study and their diagnosis was confirmed based on histological appendectomy findings. Data analysis was done using IBM SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, New York, United States), receiver operating characteristic (ROC) curve, and chi-square test as required. p-value of <0.05 was considered statistically significant. Results Out of the 320 patients with suspected AA, WBC had a p-value of 0.8 (insignificant). A total of 228 patients who had elevated WBC had confirmed histological diagnosis of AA, and 152 patients who were tested for CRP and had elevated levels had confirmed histological diagnosis of AA. CRP had a p-value of 0.04 (significant). However, when the ROC curve was used as evidence to see which was a better test, WBC and CRP both had a low area under the curve (AUC), which proved that they were not the most accurate diagnostic marker in diagnosing AA. However, CRP was slightly better than WBC. A total of 266 patients underwent USG abdomen and it had a p-value of 0.4 (insignificant), while 118 patients underwent CT scan, which had a p-value of 0.01 (significant). CT abdomen was statistically proven as a better radiological investigation. Also, when the ROC curve was used to compare USG and CT abdomen, CT again proved to be a better radio diagnostic method for AA. Conclusions From our study, it can be concluded that CRP is better than WBC in ruling in appendicitis and CT abdomen is better than USG in diagnosing appendicitis, but CT abdomen is only next to histological diagnosis in confirming AA. Hence, we recommend doing CRP as the primary laboratory marker for suspected cases of AA. CT abdomen is the ideal imaging modality in cases of suspected AA where clinical examination, laboratory values, and ultrasound examination are inconclusive.

Budd-Chiari syndrome secondary to retro-hepatic vena cava web: An unusual cause of epigastric pain.

Epigastric abdominal pain is a common indication for consultation. In the majority of cases, medical history, clinical examination and routine biological exams allow for an easy diagnosis. Sometimes the symptomatology is unusual, in which case it is essential to perform a complete clinical examination and to use various imaging techniques to search for eventual atypical causes. Membranous obstruction of inferior vena cava is a rare cause of such a phenomenon. We describe a Budd-Chiari syndrome caused by membranous obstruction of inferior vena cava in a 66-year-old woman with no medical history as a rare cause of epigastric abdominal pain. We will describe this clinical experience in the light of the literature and point out the contribution of radiological imaging in the diagnosis of this rare pathology.

Unusual case of urothelial carcinoma disguised as xanthogranulomatous pyelonephritis and causing reno-colic fistula: Case report and review of literature.

Xanthogranulomatous pyelonephritis is a rare and aggressive form of chronic pyelonephritis, it can occur at all age groups but is more common in women than in men, supposedly relating to the increased incidence of urinary tract infections and chronic nephrolithiasis in woman. Computed tomography (CT) findings are very helpful in making the correct diagnosis, but the definitive diagnosis is still based on histology, as there are many differential diagnoses such as renal cell carcinoma and renal tuberculosis. The complications of this type of pyelonephritis are due to the involvement of adjacent organs. The most frequent ones are Psoas abscess, perinephric abscess, and sepsis. Nephrocutaneous and renocolic fistulas are less common. We report a case of a 61-year-old male, who presented to emergency for left-sided lumbar pain for whom radiological investigations confirmed a renocolic fistula complicating xanthogranulomatous pyelonephritis. The diagnosis of XGP was proven by histopathological examination of the nephrectomy specimen slides, but there was also association with an underlying malignant squamous differentiation consistent with urothelial carcinoma, which was not evident on CT. XGP is a rare variant of chronic pyelonephritis with known imaging features. The treatment of choice is nephrectomy and histopathological examination is required for final diagnosis, as there may be associated renal malignancy.

Case of recurrent Achromobacter xylosoxidans bacteraemia and PICC (peripherally-inserted central catheter) line infection in an immunocompromised patient.

BACKGROUND: This report describes recurrent A. xylosoxidans bloodstream and PICC (peripherally-inserted central catheter) line infection in an immunocompromised patient. PRESENTATION OF CASE: A 64-year-old female with acute promyelocytic leukaemia presented during a non-neutropenic febrile episode, and A. xylosoxidans was isolated from multiple PICC and peripheral blood cultures, and from the tip of the line on removal. The patient was treated with meropenem and a new PICC line was inserted after sterile blood cultures. Six weeks later, she represented with A. xylosoxidans from multiple cultures from the line. She was treated with piperacillin-tazobactam and the line was removed. There was no evidence of deep-seated infection. Further discussion revealed that the patient was using a sponge to clean, and a sleeve to cover her PICC-line while bathing. A. xylosoxidans was cultured from both the sponge and the swab. Whole Genome Sequencing performed on two blood culture isolated and both environmental isolates confirmed all four isolates were indistinguishable. The patient was advised not to use the sponge/sleeve in future and we have incorporated specific advice in this regard into our patient information. DISCUSSION: Achromobacter xylosoxidans is an aerobic, non-lactose fermenting gram-negative bacillus usually considered an opportunistic pathogen. It is associated with infection in immunocompromised patients, and is an emerging pathogen in catheter-related infections, sometimes associated with contaminated water. CONCLUSION: This case of recurrent A. xylosoxidans line infection highlights diagnostic and management challenges associated with catheter-related infections. Treatment is challenging because of intrinsic and acquired resistance mechanisms. Empiric treatment with anti-pseudomonal penicillins or carbapenems with line removal is typically required.

The Effect of Annealing Temperatures on Selected Properties of WC/C Coatings, Deposited Using Hexacarbonyl Wolfram in an N2-SiH4 Atmosphere.

In this paper, we present the results of an experimental study on WC/C coatings, deposited by using plasma-enhanced chemical vapor deposition in an N2-SiH4 atmosphere, annealed at temperatures of 200, 500 and 800 °C, in which the hexacarbonyl of W was used as a precursor. During the experiments, the topography, chemical composition, morphology, as well as selected mechanical properties, such as hardness, Young's modulus, and coefficient of friction of the WC/C coatings were analyzed. Annealing without the protective atmosphere in the mentioned temperatures caused a decrease in hardness (up to 15 ± 2.7 GPa). In addition, the coefficient of friction value increased only to 0.37 ± 0.03.

Melioidosis-related mycotic aneurysm: Three cases.

BACKGROUND: Melioidosis-related mycotic aneurysm (MA) is rare but a potentially life-threatening disease with high morbidity and mortality rate. CASE PRESENTATION: We report a case series of mycotic aneurysm caused by Burkholderia pseudomallei and the subsequent outcomes. Here, we illustrate their clinical characteristics, laboratory results, radiological findings, mode of therapies and clinical outcomes. CONCLUSION: Melioidosis-associated MA may manifest in an atypical presentation. Its outcome is often lethal if antimicrobial therapy and surgical intervention are not offered promptly.

Biomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterised by organ failure(s), high short-term mortality, and, pathophysiologically, deranged inflammatory responses. The extracellular matrix (ECM) is critically involved in regulating the inflammatory response. This study aimed to determine alterations in biomarkers of ECM turnover in ACLF and their association with inflammation, organ failures, and mortality. METHODS: We studied 283 patients with cirrhosis admitted for acute decompensation (AD) with or without ACLF, 64 patients with stable cirrhosis, and 30 healthy controls. A validation cohort (25 ACLF, 9 healthy controls) was included. Plasma PRO-C3, PRO-C4, PRO-C5, PRO-C6, and PRO-C8 (i.e. collagen type III-VI and VIII formation) and C4M and C6M (i.e. collagen type IV and VI degradation) were measured. Immunohistochemistry of PRO-C6 was performed on liver biopsies (AD [n = 7], ACLF [n = 5]). A competing-risk regression analysis was performed to explore the prognostic value of biomarkers of ECM turnover with 28- and 90-day mortality. RESULTS: PRO-C3 and PRO-C6 were increased in ACLF compared to AD (p = 0.089 and p <0.001, respectively), whereas collagen degradation markers C4M and C6M were similar. Both PRO-C3 and PRO-C6 were strongly associated with liver function and inflammatory markers. Only PRO-C6 was associated with extrahepatic organ failures and 28- and 90-day mortality (hazard ratio [HR; on log-scale] 6.168, 95% CI 2.366-16.080, p <0.001, and 3.495, 95% CI 1.509-8.093, p = 0.003, respectively). These findings were consistent in the validation cohort. High PRO-C6 expression was observed in liver biopsies of patients with ACLF. CONCLUSIONS: This study shows, for the first time, evidence of severe net interstitial collagen deposition in ACLF and makes the novel observation of the association between PRO-C6 and (extrahepatic) organ failures and mortality. Further studies are needed to define the pathogenic significance of these observations. LAY SUMMARY: This study describes a disrupted turnover of collagen type III and VI in Acute-on-chronic liver failure (ACLF). Plasma biomarkers of these collagens (PRO-C3 and PRO-C6) are associated with the severity of liver dysfunction and inflammation. PRO-C6, also known as the hormone endotrophin, has also been found to be associated with multi-organ failure and prognosis in acute decompensation and ACLF.

Small Semantic Networks in Individuals with Autism Spectrum Disorder Without Intellectual Impairment: A Verbal Fluency Approach.

Individuals with Autism Spectrum Disorder (ASD) experience a variety of symptoms sometimes including atypicalities in language use. The study explored differences in semantic network organisation of adults with ASD without intellectual impairment. We assessed clusters and switches in verbal fluency tasks ('animals', 'human feature', 'verbs', 'r-words') via curve fitting in combination with corpus-driven analysis of semantic relatedness and evaluated socio-emotional and motor action related content. Compared to participants without ASD (n = 39), participants with ASD (n = 32) tended to produce smaller clusters, longer switches, and fewer words in semantic conditions (no p values survived Bonferroni-correction), whereas relatedness and content were similar. In ASD, semantic networks underlying cluster formation appeared comparably small without affecting strength of associations or content.

Segmental testicular infarction, a rare complication of epididymo-orchitis.

Segmental infarction of the testicle secondary to epididymo-orchitis is a rare condition which can be difficult to diagnose and can lead to loss of the testis. We report a case of a 72-year-old man who presented with two weeks of worsening pain of his left testis despite oral antibiotic treatment for epididymo-orchitis. A testicular ultrasound initially revealed a suspected intra-testicular abscess. Despite intravenous antibiotics, his symptoms worsened. A repeat ultrasound demonstrated an increase in size of the lesion and a decision was made to take him to theatre. Intra-operative findings instead revealed a segmental area of testicular infarction requiring debridement.

Best evidence topic: Can acute appendicitis manifest with normal inflammatory markers?

A best evidence topic has been constructed using a described protocol. The three-part question addressed was: for patients with suspected acute appendicitis can normal inflammatory markers rule out the diagnosis? Altogether 151 papers were found using the search strategy reported below. Seven were identified to provide the best evidence to answer the question. The author, journal, date, and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. In conclusion, six out of seven papers are more in favour with the concept that normal inflammatory markers cannot effectively rule out the diagnosis of acute appendicitis.