Archives of Advances in Biosciences

     Occurrenceofoxidative stress (OS) following in vitro culture is inescapable. Therefore, the aim of the present study was to determine the efficacy of Coenzyme Q₁₀(CoQ₁₀) supplementation medium on developments and Total Antioxidant Capacity (TAC) of mouse vitrified pre-antral follicles. Fresh and vitrified-warmed isolated preantral follicles from ovaries of 14-16 days-old mice were cultured in supplemented α- MEM medium with or without CoQ₁₀.On the twelfth day of culture period,ovulation was induced by adding 1.5 IU/ml human Chorionic Gonadotropin (hCG). Rates of survival, antrum formation and developmental stages of released oocytes (GV, MI, MII) were evaluated. Separately,total antioxidant capacity (TAC) levels were measured at initial time, 24, 48, 72 and 96 hours of culture periodby ferric reducing/antioxidant power (FRAP) assay. The results showed that the mean diameter and rates of survival, antrum formation, ovulation and MII oocytes of fresh and vitrified-warmed isolated preantral follicles with pretreatment of CoQ₁₀ were significantly higher than those of respective groups without pretreatment ofCoQ₁₀. TAC levels significantly increased up to 96hours in fresh and vitrified-warmed preantral follicles with pre-treatment of CoQ₁₀ compared with thosewhich were cultured without CoQ₁₀. Supplemented culture medium with CoQ₁₀ promotes TAC levels and development of both fresh and vitrified-warmed isolated preantral follicles.

Male infertility is a distressingly common condition affecting about 1 in 20 of the male population. In a majority of the cases, the male partner produces sufficient numbers of spermatozoa to achieve fertilization but there are functional defects in these cells that prevent conception from occurring. In this study, the effects of Wi-Fi radiation on spermatogenesis, testes and testosterone of large white male rats were studied, and also hydro alcoholic extract of sea buckthorn fruit were used as a protective agent against the effects of Wi-Fi radiation, and the comparative study was done.For this study 60 white male laboratory rats weighing 200-250 g were selected then tested in good conditions of light and food. The mice were randomly divided in terms of Wi-Fi Radiation and received gavage Sea buckthorn into 6 out of groups of 10.It was found that in the groups that had received Wi-Fi radiation, waves did not affect sperm count, testes weight, testosterone and testicular tissue, but it caused a significant decrease in fertilized sperm motility, and sea buckthorn extract could work as a protective agent against the radiations. According to the results of this research, it can be the probability that Sea buckthorn extract, having antioxidant substance can prevent destructive effects of waves that cause free radicals and having vitamin E improves sperm quality.

Generally ICU patients are in critical status and need long stay in ICU. Pulmonary rehabilitation program (PRP) is considered as an important tool to improve outcome and shorten the length of stay in ICU. The aim of this study was to investigate whether PRP can affect outcome and duration of hospitalization in ICU patients. This study was performed in medical ICU of Labafi Nejad hospital, Tehran, Iran during 2012 and 2013. All of patients who had more than one day stay in ICU were included in the study. They underwent PRP. We compared length of stay, mortality rate and number of hospitalized patients within 2 years in patients with PRP and patients without PRP. In 2012, 155 patients and in 2013, 173 patients were admitted in ICU.  Admission period was 15 ± 2.7 and 11 ± 2.1 days, respectively (p< 0.001). Pulmonary physiotherapy showed no effect on patients’ outcome in which during 2012, 94 patients were discharged and 61 patients were died and in 2013, 98 patients were discharged and 64 patients were died (p=0.9). Our study shows that PRP can shorten hospitalization time which can indirectly decrease hospitalization costs but there is no effect on overall survival.

        The most important characteristics of PTSD, as an anxiety disorder, are memory disorders and hippocampus is one of the essential structures which plays a critical role in PTSD memory disorders. Traumatic events cause apoptosis and alter the expression of neurotrophic factors in hippocampus. The aim of this study is to evaluate the effects of β-Estradiol on behavioral responses in PTSD and to study its biochemical and histological mechanisms.

We used single prolonged stress (SPS) to develop PTSD in rats. The day after, the rats received electrical foot shock within shock chamber. One week later, in order to test the conditioned fear responses, the freezing behavior of rats were examined for 5 continuous days, as they were placed back in the chamber without any shock. Animals received multiple injections of β-estradiol or sesame oil, immediately after shock and also on a daily basis through the seven days prior to the test. Hippocampal cell count was implemented after cresyl violet staining. We measured BDNF protein levels by ELISA kit.

Main findings of this study confirmed that exaggerated fear response is observed in PTSD group as compared with control group and β-estradiol administration reduced these exaggerated behavioral responses. We found out that SPS decreases the density of cells in hippocampus and this effect is partly corrected by β-estradiol; β-estradiol increased BDNF protein level in hippocampus as compared with PTSD group; BDNF protein level was negatively correlated with freezing response in both SPS+β-estradiol and SPS+sesame group.The results of this study is consistent with the hypothesis that decreased expression of BDNF contributes to memory impairment in PTSD and up regulation of BDNF by β-estradiol plays a role in memory treatment.

     Protein A is a commercially important protein in biotechnological and medicinal applications. The great value of this protein and its applications in genetic and protein engineering and microbial researches as well as the growing use in biochemical industries, biotechnology, medicine and pharmacology, highlight the importance of the present study. In this survey the encoding genes of full-length and truncated forms of protein A were expressed in E. coli under an optimized expression condition. Optimization of the culture conditions resulted in an increase in expression and secretion of both forms of the protein, the pattern of expression and secretion levels for two forms was completely different. A minimum of 10-fold higher expression was observed for the truncated protein in comparison to that of the full-length recombinant form. Hydropathy plot of both forms of proteins showed that the missing domains in the truncated form contain groups of amino acids with high hydrophobicity score. Deletion of the terminal region could led to a higher expression level of the recombinant protein in E. coli. The function of these two proteins was studied using ELISA, which showed a higher activity for the truncated form for binding to IgG, compared to the full-length protein.

Poly vinyl alcohol/Chitosan nanofibrous mat were prepared by electrospinning method with suitable pore sizes as potential matrices for soft tissue engineering. The designed scaffolds by electrospinning method evaluated by differentanalyses such morphological, mechanical, and cellular analysis.Microscopic results showed diameters of poly vinyl alcohol/Chitosan nanofibers were approximately 150 nm. Mechanical investigations illustratedstress - strain curve of poly vinyl alcohol /chitosan mat indicate good flexibility with average strain and good percentage of yield stress. The cellular resultsrevealthat addition of chitosan to poly vinyl alcohol enhances viability and proliferationof fibroblast cells, which increases the biocompatibility of the scaffold. In fact, addition of a smallpercentage of chitosan to the poly vinyl alcoholproved to be a promising approach for designof a scaffold.

     The potential indoor air impacts of burning candles have drawn increased attention in recent years.  Burning paraffin waxes itself, regardless to wick and the essence, produce some allergens and even carcinogenic compounds. Further biorefining of petroleum paraffin wax with proper bacteria is one of the proposed resolutions to decrease the health threat. Therefore in this study Iranian heavy crude oil sample were screened for the best isolate to reach the target. Manual culture and plate count method and screening were done in MSM medium supplemented with paraffin wax as the sole source of carbon and energy in 40°C and 150rpm. The growth curve of the best isolate was depicted through spectrophotometry during 24 hours. Then the isolate was characterized by biochemical test and molecular identification using 16srRNA. The spore forming, biosurfactant producing bacterium was identified as Bacillus cereus. Gas chromatogaraphs revealed the efficient degradation of long chain paraffin wax with the selected Bacillus cereus into 15 to 25 carbon length n- alkanes. The high physicochemical endurance of this bacterium including salinity tolerance from 0.5to 15 percent, pH from 4 to 10 and temperature growth range from 40 to 65°C, makes it a decent choice for industrial and environmental approaches.

   Reteplase is a part of tissue Plasminogen Activator (t-PA) used for theremoval of thrombi in blood vessels. In the present study we express the reteplase genein Escherichia coli TOP10 and then its thrombolytic activity was measured. The recombinant plasmid pBADgIIIA was transformed into the competent Escherichia coli TOP10and then transformed bacteria was seeded into bioreactor containing 1.5 L LB medium and induced by 0.02% L-Arabinoseat 37°C, pH 7, and 180 rpm until OD 600 of 0.6 was reached.Samples were analyzed by SDS-PAGE and western blotting andthe expression of reteplase was examined. Finally the activity of this recombinant protein was evaluated using Chromogenic Activity Assay Kit. The presence of reteplase in transformed Escherichia coli TOP10 wasexamined by western blotting which revealed that the target protein in form inclusion body was expressed as a unique band at39 and the refolded reteplase was 66KDa. The amount of protein produced was 90.5µg/mL and its activity was determined as 0.8 units. In this study, the expression of reteplase in Escherichia coli TOP10 wasscaled up under optimum condition. Furthermore we earned reteplase with partially suitable thrombolytic activity.

     Nucleostemin (NS), a stem cell-abundant nucleolar protein, is critical for maintaining the self-renewal and proliferative properties of normal and cancerous stem cells. Recent data suggests that NS signaling is important for proliferation of T-cells and leukemia cells. This study was conducted to verify the role of NS in pathogenesis and treatment of T-cell acute lymphocytic leukemia (T-ALL). Our results revealed that RNA interference-mediated NS silencing primarily affected clonogenicproperty of T-ALL cells by limiting their self-renewal potential in vitro.These effects were accompanied with inhibition of proliferation and early apoptosis in Jurkat cells (p53-null) while late apoptosis in Molt-4 (p53 functional) T-ALL cells. Collectively, our results suggest that NS is a critical regulator in self-renewal and apoptosis of differentT-ALL cells. This suggests therapeutic potential of this gene in leukemia.

     Cancer is the second important reason of mortality in the world. In this regard melanoma was accounted as the most aggressive type of coetaneous cancer. Among drug extracted from natural products from marine organisms have been focused investigations related to chemotherapeutic agents derived from echinoderms such as sea cucumbers and starfish.  In the present study, cytotoxic and apoptosis inducing potential of Persian Gulf Brittle Stars dichloromethane extract were evaluated against melanoma cancers. In this study, anti-proliferative effect of brittle stars Dichloromethane extract on B16F10 melanoma cells examined by MTT assay and morphological characterization and death inducing effect of Annexin-PI and PI flow cytometry. The data analysis was performed by SPSS software and p<0/05 were considered significant. The dichloromethane extract of brittle star revealed significant cytotoxic effect on B16F10 melanoma cells with IC₅₀= 31 µg/ml which is stronger than inhibitory effect of methanol extract on melanoma cell growth. In addition, brittle star dichloromethane extract recruited apoptotic pathway in the response of 31 µg/ml treatment.  This study showed that certain concentrations of dichloromethane brittle stars possess cytotoxic activity that can be used as an anticancer agent used in clinical trial due to cell growth inhibition and apoptosis induction which offer therapeutic investigations of dichloromethane brittle star extract as complementary for melanoma treatment and prevention.

      Flour dust has been introduced as one of the effective factors in the prevalence of respiratory disorders among the workers of the flour production factories. The purpose of the present study is to examine the effects of this pollutant on the pulmonary functions and survey the prevalence of respiratory symptoms among workers of flour production factories in Arak, Iran.  Exposure to flour dust is used to classify subjects into exposed (38 male workers of production plant) or unexposed groups (37 male employee from administrative section). Exposure level to flour dust, the prevalence of respiratory symptoms and pulmonary function in two group were studied using air sampling (based on method NIOSH 0600), a researcher made questionnaire on respiratory symptoms and Spirometer, respectively. The results indicated that workers of the production plant are exposed to high concentration of flour, which causes a decrease in the ratio of FEV1 / FVC compared to the unexposed ones. Among study respiratory symptoms, subjects had reported significantly more sputum secretion than that in control group. Furthermore intervening parameters, including age, work experience, body mass index and smoking didn’t show a significant effect on the pulmonary function of the individuals. Exposure to flour dust concentration with higher than threshold level values causes a decrease in workers respiratory capacity. Therefore, it is recommended that the reduction of both exposure risk and the 8-hour time-weighted average concentration of flour dust should be considered.

Job satisfaction of employees is one of the most challenging concepts in any organization and is the basis for many of the policies and management strategies to increase productivity and efficiency. It is influenced by many factors including environmental and personal factors, income, nature and social status of the job, organizational prestige, promotion, job security, lack of role ambiguity, and physical job conditions Co-workers. This study was carried out to determine the factors affecting job satisfaction employees of Semnan health center's to meet the challenges and increase efficiency. This is a cross-sectional study carried out in 2013, over 93 employees with a employment history of over 2 years. Method and data collection was through job descriptive inventory (Job Descriptive Index); data was collected and analyzed using SPSS16. The results of questionnaire analysis in seven items regarding job satisfaction, show satisfaction supervision and leadership (77.2%), management policy (77%), job stability (63.4%), environmental conditions (59.6%), cross-relation between Co-workers (58.6%), salary and benefits (53.4%) and opportunities for growth, development and promotion (53.2%). Based on evaluated items, the overall job satisfaction in this study was moderate. Thus, in terms of job satisfaction, it seems that different factors affective in different ratios. Job satisfaction is not only very important by itself, but also important concerning its impact on other aspects of the job attitude. In fact, by increasing job satisfaction, other aspects of job attitudes such as organizational commitment, job involvement and organizational atmosphere can be improved. This point can also be seen in proposed models and research carried out by professionals in this field.

      The somatic and metabolic changes due to menopause can result in numerous symptoms including psychological symptoms. This study compares the effectiveness of Gabapentin vs. Fluoxetine in treatment of psychological symptoms of menopause. Methods:Eighty menopausal women with history of hot flashes and predefined psychological symptoms participated in a cross-over study conducted at the Amir-Al-Momenin hospital, Semnan, Iran.  Participants were randomly divided into two groups: A and B. The study included two rounds of treatment, each 4 weeks long, separated by a two-week washout period. In the first round of treatment, group A was treated with Fluoxetine 20mg/d and group B with Gabapentin 300 mg/d. In the second round of treatment, group A received Gabapentin while group B received Fluoxetine (cross-over).All participants were asked to fill out the "Green Climacteric Scale" questionnaire at the beginning of the study and also following each round of treatment. They were also asked to monitor and keep track of the side effects of the medications by filling out another form. There was no significant difference between the two groups in age, body mass index, and age at menopause (p>0.05). The severity of irritability, fatigue, difficulty in concentrating, difficulty in sleeping, nervousness, and palpitation reduced to a significantly greater extent when the participants were treated with Gabapentin than when they were treated with Fluoxetine. Side effects (tremor) developed in only 2 Fluoxetine users and 2 Gabapentin users during the first 4 weeks of treatment. Our findings suggest that Gabapentin is more effective in alleviating the psychological symptoms of menopause than Fluoxetine. Thus, we recommend Gabapentin 300 mg/d for menopausal women who primarily complain about psychological symptoms, or those with contraindication to hormonal therapy.

       MDMA generally known as ecstasy, have deleterious effects on the serotonergic neurotransmitter system. Recent findings suggest that the liver and brain are major target organs of MDMA-related toxicities. Although most research is being dynamically performed on brain, however, the molecular mechanisms by which MDMA elicits adverse effects in both organs are poorly undrestood.The present study was performed to obtain evidence for molecular mechanism of apoptosis involved in MDMA-induced hepatotoxicity in rat liver after MDMAadministration. Moreover, the antagonistic effect of pentoxifylline was assessed on hepatotoxicity after MDMA administration. In this experimental study, sample size and power in each group were calculated as 10 rats with 95% confidence level and 5% confidence interval. In the study, four experimental groups were selected including Control Normal, MDMA, MDMA+PTX and PTX+MDMA. MDMA was dissolved in PBS and intraperitoneally injected three doses of 7.5mg/kg with two hours gap between doses. Pentoxyfilline also was injected as 100mg/kg, simultaneously with third dose of MDMA. After treatment, total RNA was isolated from liver tissue (5mg). Absorbance at 260nm, 280nm and 230nm were measured and immediately reverse transcription was performed. Included target genes were BAD and BCL_-XL as pro-apoptotic and anti-apoptotic gene, respectively. After set up and validation, Real-Time PCR were performed and obtaining data were statistically analyzed to determine significantly differences between groups. Using Real-Time quantitative PCR results, BCL-_XL gene expression ratio significantly increased in MDMA+PTX group. Moreover, BAD gene expression ratio increased and up-regulated in PTX+MDMA group (P-value <0.001).Our study focused on molecular mechanism of MDMA in programmed cell death using gene expression quantification of a pro-apoptotic and anti-apoptoic gene in MDMA-induced hepatotoxocity. The results shown MDMA prompted apoptosis in liver and pentoxifylline protects hepatotoxicity after and befor taking MDMA.

Streptococcuscus Beta Hemolytic Group A is the most important pathogen causing which may lead to purulent and non purulent angina. Rheumatic fever is the most important complication that is the cause of 30% to 40% of cardiac disease and disablement. This study was performed to evaluate prevalence of Streptococcuscus Beta Hemolytic Group A and estimate role of clinical findings in children with Streptococcuscus angina diagnosis. antibiotic resistance was also assessed evaluated in the patients with bacterial pharyngitis. Throat culture was performed on 104 patients referred to Amiralmomenin hospital of Semnan at the age range of 5 to 15 years having angina without begin on antibiotic treatment after the completion of the questionnaire. A frequency of 1% have been assessed for Streptococcuscus Beta Hemolytic Group A, coagulase -positive Staphylococci and non-group A Streptococcuscus frequencies were 10.6% and 17.3% respectively. 100% of patients had pharyngeal erythema, 72% had fever, 55% had exudates and 52% had cervical adenopathy. The diagnosed Streptococcuscus was sensitive against penicillin, erythromycin and amoxicillin and resistant against cotrimoxazole. In examining Staphylococcus aureus antibiotic-resistance, only 40% of cases were sensitive to clindamycin and 40% were also sensitive to vancomycin. Very low frequency of group A Streptococcuscus has undermined the routine use of antibiotic and show that the clinical based diagnosis alone is not reliable and rational use of antibiotics requires the use of other diagnostic methods such as throat culture and rapid antigen test (RATs). Also in analyzing coagulase -positive Staphylococci antibiotic resistance, we can see increased cases of resistance against neomycin and clindamycin which indicates the necessity of rational treatment of patients afflicted by strep to coccal infections.

Extremely low frequency (ELF) and Radio frequency (RF) electromagnetic field may affect biological systems by raising generation free radicals by decline activities of glutathione peroxidase dismutase or increase in the lifetime of free radicals with inhibited pretreatment of cells antioxidant like that alpha tocopherol. ELF and  RF electromagnetic  field maycan damaged DNA  with raising level  hydroxyl radicals in cells and  it is  can interact DNA and form mainly 8-hydroxy-2′–deoxyguanosine( 8-OHdG) adducts. Many study showed   Electromagnetic field radiation(EMF) can change gene expression and conformation of protein. It may declineexpression of some genes such as superoxide dismutase orraise expressionof certain genes such as Hsps (heat shock proteins). ELF and RFelectromagnetic field   can effects on homeostasis Ca²⁺ and alteration in important cellular and molecular processes such as differentiation, proliferation, gene expression, cytoskeletal reorganization and metabolism. Use of radio frequency electromagneticfield onsatellite jamming in Iran and some country may can harmful to human health and it could be a risk factor for cancer.

The rapid expansion in world production of palm oil over the last three decades has attracted the attention of the oils and fats industry. Oil palm gives the highest yield of oil per unit of any crop. Palm oil is the major oil produced, with annual world production in excess of 50 million tonnes. Throughout the world, 90% of palm oil is used for edible purposes (e.g., margarine, deep fat frying, shortening, ice creams, and cocoa butter substitutes in chocolate); the remaining 10% is used for soap and oleo chemical manufacturing (fatty acids, methyl esters, fatty nitrogenous derivatives, surfactants and detergents). Two distinct oils are produced by oil palms (palm kernel oil and palm oil), both of which are important in world trade. Palm oil contains 50% saturated fatty acids. The saturated fatty acid to unsaturated fatty acid ratio of palm oil is close to unity and it contains a high amount of the antioxidants, β-carotene, and vitamin E. Palm oil contains a high proportion of palmitic acid as well as considerable quantities of oleic and linoleic acids. The physicochemical properties, fatty acid profile and nutrition in palm oils are reviewed.

   Proteins are fundamental components of cells which mediate many essential biological processes. Proteomics is a rapidly growing field for the study of proteome, the protein complement expressed by the genome of an organism or cell type. The large-scale analysis of proteins leads to a more comprehensive view of molecular and cellular pathways that improves the overall understanding of the complex processes supporting the living systems. The analysis of proteome is significantly challenging due to high dynamic range and difficulties in assessment of low abundance proteins and the absence of efficient purification and identification techniques. A variety of methods have been utilized for protein studies including gel-based techniques, protein microarrays, mass spectrometry-based approaches such as MALDI and SELDI, high and ultra-performance liquid chromatography and fourier transform ion cyclotron resonance mass spectrometry. NMR spectroscopy and X-Ray crystallography methods are also used for structural study of proteins. This review aims to give a brief overview of some of the above techniques and their most recent advances. We also introduce Proteominer, a recent protein enrichment technology for the exploration of the entire proteome content

      The genus Ebola virus first was recognized in 1976, when two outbreaks occurred in Zaire and Sudan. Ebola virus disease (EVD) is a highly contagious disease that can affect both human and nonhuman primates: Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Côte d’Ivoire ebolavirus (CEBOV), Bundibugyo ebolavirus (BEBOV) and Reston ebolavirus (REBOV) are five members of the Filoviridae family that can cause haemorrhagic fever. EVD is transmitted by direct contact with contaminated blood or other biological fluids of the infected animals such as chimpanzees, gorillas, fruit bats, monkeys, forest antelope and porcupines found ill or dead or in the rainforest. Ebola is responsible for different clinical futures that can be ranged from fever, headache, arthralgia, myalgia, abdominal pain, anorexia and vomiting to severe respiratory disorders, viral hemorrhagic fever, cardio-vascular disorders and hypovolaemic shock.  Although there is no specific treatment for EVD, considerable advances like use of monoclonal antibody, intefron and Favipiravir/T-705 as effective chemotherapeutic agent in treatment of EBV have been made. To date, 25 outbreaks of EVD have been reported. Hence, EVD as a zoonotic disease should be more focused not only in endemic area but also in throughout the world. Awareness of the disease and routes of transmission and also continuous surveillance to combat disease and outbreaks is necessary.

Dear Editor,

We read with interest the paper, “The effect of food service system modifications on staff body mass index in an industrial organization”[1]. We noticed several substantial issues with data and calculations, calling into question the randomized nature of the study and validity of analyses.The distribution of baseline weight was significantly differentbetween groups (p-value = “0.00”). We replicated the test using reported means and standard deviations (SDs) andobtained a p-value of approximately 1.9*10^-17. It is extraordinarily unlikely that any variable would be that different between two groups if allocation was truly random. Even it was truly random, the stated method of “the samples were randomly divided into two groups”[1] does not describe the “method used to generate the random allocation sequence” and the “type of randomization; details of any restriction (such as blocking and block size)” details specified by Consolidated Standards of Reporting Trials (CONSORT)[2].Given the large difference in baseline weights, it is unusual that the difference in baseline body mass index (BMI) between groups is not more significant (p=0.032), raising the question of what the groups’ distributions of height were. Both groups have 30 males (58.8%), so sex differences are unlikely to explain this discrepancy. Height was not explicitly reported, but it was possible to estimate height utilizing geometric means from body weight and BMI[3,4]. We calculated the baseline control group geometric mean as 2.04 cm taller than the test group. These calculations also suggest the control group shrunk by 1.26 cm while the test group grew by 1.52 cm over the study. Neither change is explained by rounding error nor seems plausible for adult subjects over 40 days.Because there were no SDs of the change scores reported, we were unable to replicate the reported p-value (0.318) for the between-group test of weight change exactly. However, we were able to consider the pre and post-intervention SDs and calculate possible SDs of within-group change scores for a range of pre-post correlations. The largest p-value possible was 0.1282, calculated when each group had perfect negative pre-post correlation (correlation=-1), which is unlikely. If there was no or a positive correlation, the p-value would be much smaller (p=0.0449 when correlation=0 for each group) and plausibly indicates a significant difference between groups. Therefore, although the published results are impossible the correct analysis could make the intervention appear more effective than reported.The results section describes an initial sample size of 116 with 14 dropping out (p. 115). The tables report the remaining sample size to be 102, but the body of the text reports 101 subjects remained until study completion. It is unclear which values were correct; this lack of clarity also fails CONSORT guidelines[2].Considering that the reported findings are essentially impossible given the stated study design, we encourage the authors to explain the treatment allocationand make the raw data available, or the journal to act according to the Committee on Publication Ethics[5] in situations where findings are unreliable