Anopheles gambiae s.l. to bendiocarb and malathion, at the phenotypic and molecular levels, in different eco-epidemiological settings in Cameroon. Anopheles gambiae s.l. mosquitoes were collected from four eco-epidemiological settings across the country and their susceptibility level to bendiocarb and malathion was determined using WHO tubes bioassays. The ace-1 target site G119S mutation was screened by PCR. Reverse Transcription quantitative PCR 3-plex TaqMan assays were used to quantify the level of expression of eight genes associated with metabolic resistance. Resistance to malathion and/or bendiocarb was recorded in all study sites except in mosquitoes collected in Kaélé and Njombé. The Ace-1 (G119S) mutation was detected in high frequencies (>40%) in Kékem and Santchou. Both An. gambiae and An. coluzzii were detected carrying this mutation. The cytochrome P450s gene Cyp6p3 associated with carbamate resistance and the glutathione S-transferase gene Gste2 associated with organophosphate resistance were found to be overexpressed. Genes associated with pyrethroid  and organochlorine  and cuticle resistance (Cyp4g16) were also overexpressed. The rapid spread of resistance to organophosphates and carbamates could seriously compromise future control strategies based on IRS. It is therefore becoming important to assess the magnitude of bendiocarb and malathion resistance countrywide.The spread of pyrethroid resistance in malaria vectors is a major threat affecting the performance of current control measures. However, there is still not enough information on the resistance profile of mosquitoes to carbamates and organophosphates which could be used as alternatives. The present study assessed the resistance profile of  Since their discovery, synthetic insecticides have been largely used for the prevention of vector-borne diseases, due to their high efficacy and ease of use . The figPyrethroids, due to their high efficacy against insects and low toxicity to mammals, including humans, are the only insecticide recommended for bed net impregnation . Over 3 An. gambiae s.l. [Carbamates and organophosphates are considered as possible alternatives for controlling pyrethroid-resistant mosquitoes ,13. In oiae s.l. ,24. StilAnopheles gambiae s.l. to bendiocarb (carbamate) and malathion (organophosphate) in four epidemiological settings in Cameroon and to explore the molecular basis of resistance.The present study aims to characterize the resistance status of Anopheles specimens from laboratory strains (Kisumu and Ngousso) and 2490 field specimens from Kékem (n = 160), Njombé (n = 200), Belabo (n = 200), Kaélé (n = 400), Tibati (n = 400), Bertoua (n = 570) and Santchou (n = 560) were exposed to determine their susceptibility profile against bendiocarb and malathion insecticide. The two laboratory strains were all susceptible to bendiocarb and malathion with mortality rate of 100%, demonstrating that the impregnated paper was good. The susceptibility profile was year- and insecticide-dependent in each locality . Samples tested in 2020 in Bertoua and Tibati were found to be significantly more susceptible to bendiocarb  compared to those collected in 2019 and 2021 .In addition, the mortality rate of mosquitoes varied significantly with year, except in Santchou, where no significant difference was found regarding Bendiocab  mutation was detected in all sites. In Njombé the G119S mutation was detected mainly in bendiocarb and malathion survivors (75.5–100.0%) and at a very low frequency (4.5%) in the unexposed population. In Kékem bendiocarb survivors showed a frequency of 84.6% and unexposed mosquitoes a lower frequency (41.1%). The Bélabo population presented a frequency of 54.1% and 72.3% in bendiocarb and malathion survivors, respectively; it was also detected in unexposed mosquitoes in a frequency of 10.25%. In Tibati, a frequency of 81.3% was recorded in Bendiocarb survivors, whereas it was not detected in unexposed mosquitoes. In Bertoua, bendiocarb and malathion survivors showed frequencies of 71.0% and 77.1%, respectively; unexposed mosquitoes exhibited a frequency of 36.1%. In the Santchou population, the mutation was found in frequencies > 85.0% in bendiocarb and malathion survivors, as well as unexposed mosquitoes .Cyp6p3, Cyp6m2, Cyp9k1, Cyp6p4, Cyp6z1, Gste2 and Cyp4g16 were among genes that were significantly overexpressed in at least one study population. More precisely, in the Njombé population . In Kékem the Cyp6m2 and Cyp9k1 genes were both overexpressed by >3.0 folds (Cyp6p4 (>10 folds) and Gste2 (>5.0 folds). In Bélabo, Cyp6p3 and Cyp6p4 were overexpressed by >1.90 folds (Cyp4g16 (>1.60 folds). In Bertoua, Cyp9k1 and Cyp6p4 were significantly overexpressed . The Santchou population showed a >1.6-fold overexpression of Cyp6z1  is in line with previous studies which indicated that this species is outpacing An. arabiensis and is gradually becoming the predominant species in the Sudano-Sahelian savannah zone [The study’s objective was to assess the distribution of carbamate and organophosphate resistance in  reports ,24,25. R reports . It is p complex ,28. Simiountries . Anophelnah zone ,30. In an effort to molecularly profile the evident carbamate and organophosphate phenotypic resistance we measured the frequencies of the Ace-1 G119S mutation, as well as the expression levels of genes associated with metabolic and cuticle resistance.An. gambiae and An. coluzzii with, however, a higher frequency in An. gambiae. A similar distribution pattern has been reported in many countries across West Africa [An. gambiae. It is possible that the Ace-1 G119S mutation in An. coluzzii may have emerged during recent years through introgression or independently. Different frequencies of the G119S allele have been reported between An. gambiae and An. coluzzii in areas of sympatry. It has been suggested that the difference in this mutation frequency could result from discrepancies in the selection pressure mosquitoes experienced in aquatic habitats [The Ace-1 G119S mutation was detected at a very high frequency in almost all sites. Studies conducted so far in Africa suggested that the presence of this mutation is mainly associated with resistance to carbamates ,18,22,31t Africa ,22. The t Africa ,25, whichabitats . Cyp6p3 was significantly overexpressed in the Bélabo population, where phenotypic resistance to bendiocarb was also detected. This particular P450 gene has been previously shown to metabolize bendiocarb [Cyp6p4 was detected. Cyp6p4 has been previously shown to metabolize malathion, as well as other organophosphates ; however, a link to resistance cannot be safely concluded, and organophosphate metabolism by Cyp6p4 could lead either to the activation of more toxic metabolites or detoxification, and the relative activation versus detoxification contribution is not clear. This is also the case for Cyp6p3 and Cyp6m2 with data for the latter pointing towards activation rather than detoxification. The glutathione S-transferase gene gste2 was found to be markedly overexpressed in the Kaélé population. Since, gste2 has been strongly linked with resistance to the organophosphate fenitrothion [Cyp6m2, Cyp9k1, Cyp6p4) and organochlorine  metabolizers [Cyp4g16, a functional oxidative decarboxylase gene known to catalyze epicuticular lipid biosynthesis and contribute to insecticide resistance via the enrichment of the CHC content, thus reducing insecticide uptake was also found to be upregulated in one population (Tibati) [In addition to the Ace-1 mutation the expression profiles of genes implicated in metabolic and cuticle resistance were assessed. Regarding carbamate resistance, ndiocarb ,34. Regabolizers . All the(Tibati) .a) is published in Kala-Chouakeu et al. [Mosquitoes were collected from seven localities in Cameroon: Kékem, Njombé, Belabo, Kaélé, Tibati, Bertoua and Santchou . A detaiu et al. .An. gambiae s.l. from different sites and susceptible strains (the An. gambiae Kisumu strain and the An. coluzzii Ngousso strain) were preserved in RNAlater™ for the characterization of the molecular mechanisms of insecticide resistance. The same sample was also used for species identification. Another subset of about 120–150 mosquitoes per population was used for insecticide bioassays; survivors after exposure to insecticide were preserved in 70% alcohol and used for the confirmation of molecular species identification and detection of G119S.The field sampling of anopheline larvae and processing was conducted during the long rainy season in all the sites. It was carried out once yearly in August 2019, August 2020 and November 2021 in Bertoua and Santchou, whereas in the remaining sites the sampling and processing of mosquitoes was performed once or twice  because of the unavailability of funds . Larval An. gambiae s.l. reared from larval collections in different sites were tested alongside the susceptible laboratory strains Kisumu and Ngousso against two insecticides  following WHO guidelines [An. gambiae s.l. females aged 3–5 days reared from larvae collected on the field were placed in batches of 20 to 25 mosquitoes per tube and left for observation for one hour. After this period, mosquitoes were transferred to four different tubes with insecticide-impregnated papers and exposed for 1 h. The susceptible laboratory strains (An. gambiae (Kisumu strain) and An. coluzzii (Ngousso strain)) were used as control to assess the quality of the impregnated papers. The number of mosquitoes knocked down by the insecticide was recorded after 1h of exposure; then, mosquitoes were fed with a 10% sugar solution and the number of dead mosquitoes was recorded 24 h post-exposure. Mosquitoes were considered resistant when the mortality rate was <90% and susceptible when the mortality rate was ≥98%, and resistance status needed further scrutiny when the mortality rate was <98% and >90% [Adult female idelines . An. gamand >90% .260/A280 ratio, indicative of sample purity, was 2.3 ± 0.05. The quality of RNA was assessed by 1.0% w/v agarose gel electrophoresis. Representative samples are shown in Using a magnetic beads-based approach with the MagSi kit , total genomic material (RNA and DNA) was extracted from 687 mosquitoes . Mosquitoes were pooled for extractions (up to N = 10 mosquitoes per pool). The quantity and purity of DNA and total RNA were assessed spectrophotometrically via Nanodrop measurements. The average NA concentration was 58.96 ± 5.4 ng/μL and the average AAn. coluzzii and An. gambiae species .Mosquitoes used for species identification included those exposed to insecticide  and some not exposed to insecticides. Mosquitoes from different years were analyzed. Species identification at the molecular level was performed using the TaqMan assays described in the Innovative Vector Control Consortium (IVCC) Vector Population Monitoring Tool (VPMT)  with modAM-CtHEX values) to allelic frequencies via the equation of the standard curve’s regression model , as described in VPMT . The peron model .Cyp6p3, Cyp6m2, Cyp9k1, Cyp6p4, Cyp6z1, Gste2, Cyp6p1) that have been strongly associated with metabolic resistance and one oxidative decarboxylase (Cyp4g16) that is implicated in cuticle resistance [TM Real-Time PCR system v1.3 (Applied Biosystems) software was used for the calculation of Ct values for each reaction.The reverse transcription quantitative PCR (qRT-PCR) 3-plex TaqMan® assays described in Mavridis et al., 2019  were usesistance . The lisUsing the method developed by Pfaff , fold-chAn. gambiae s.l. populations across Cameroon. Both Ace-1 G119S mutation and the overexpression of genes associated with carbamate/organophosphate resistance were detected. The current expansion of carbamates and organophosphate resistance could seriously compromise future malaria control measures based on the use of organophosphates and carbamates in IRS. Addressing gaps affecting malaria control by improving surveillance activities on the vector is becoming crucial to ensure the success of malaria elimination efforts in Cameroon. This study indicates the heterogeneous distribution of carbamate and organophosphate resistance in


This cross-sectional study assesses policy adherence to national guidelines for timeliness of test results communication to patients in the Department of Veteran Affairs health care system. To assess policy adherence, the VA implemented a quality measurement system for feedback and improvement. We analyzed the first full year of these measures to determine timeliness of test results communication to patients.Failure to communicate test results to patients remains a persistent problem leading to diagnosis and management delays,STROBE) reporting guideline. Data collection was implemented through the External Peer Review Program (EPRP), the VA’s performance measurement system that is used for quality improvement and benchmarking. Computerized algorithms randomly sample a set of abnormal and normal results related to 8 predetermined tests for each VA facility and each quarter , normal results (≤14 days), and all test results (≤30 days). Additionally, we evaluated 1 item from the Survey of Healthcare Experiences of Patients (SHEP) during the same timeframe .P < .05 with a 2-tailed test. Data were given to us between February and May 2021 and were analyzed between March and November 2021.We used descriptive statistics to examine EPRP and SHEP data and a Pearson correlation between the EPRP measure for all test results and the SHEP item. Using Stata version 15.1 (StataCorp), statistical analysis was conducted using a significance threshold of EPRP measures showed timely communication for 5925 of 8372 abnormal results (70.8%) ; for 9472 of 11 784 normal results (80.4%) ; and 16 479 of 20 156 (81.8%) of all test results within 30 days. Performance varied by facility; timely communication ranged between a median (range) of 71.4% (45.5%-93.9%) for abnormal results, 81.3% (52.9%-96.8%) for normal results, and 82.3% (58.5%-94.8%) for all tests . Performr = 0.30; df = 128; P < .001).In SHEP data from 213 464 patients, 17 435 patients (8.2%) said that results were never communicated, 13 456 (6.3%) said results were sometimes communicated, 33 673 (15.8%) said results were usually communicated, and 148 900 (69.8%) said results were always communicated. These findings varied by facility; for example, a median (range) of 7.6% (2.6%-23.5%) of patients reported results were never communicated, while a median (range) of 69.7% (50.7%-83.5%) of patients reported results were always communicated . The SHE6 A limitation of this study is that these data rely on documentation and do not reveal all aspects of communication quality. Despite this limitation, the data are supported by patient experience surveys. The 21st Century Cures Act requires the release of test results to patients, but communication for abnormal results requires monitoring to ensure adequate follow-up. Similar quality measures can be implemented in other health systems able to query and review electronic health record data. Given persistent care gaps, these measures should be used as accountability metrics to facilitate wider implementation of known interventions to improve the timeliness of test results communication to patients.The VA’s national performance measurement system reveals gaps in timely communication of test results to patients. Communication gaps varied by facility, emphasizing the need for local quality improvement efforts to address contextual factors impacting follow-up .


Background: Migraine is a primary headache and a complicated neurological disorder with sensory and autonomic abnormalities. Many variables, including genetic and psychological ones, contribute to migraine onset and development. Anxiety and depression are typical psychiatric comorbidities among migraineurs. This kind of comorbidity increased migraine chronicity, treatment effectiveness, and the likelihood of additional comorbidities. The purpose of this research was to determine the prevalence of depression among Saudi migraine sufferers in AlAhsa.Methods: Descriptive cross-sectional research of 101 migraine patients at King Fahd Hospital-Hofuf, AlAhsa, Saudi Arabia from May to December 2021. Depression was assessed by Patient Health Questionnaire which is a reliable tool (PHQ-9). The PHQ-9 measures the presence and severity of depression. Consider sociodemographic, clinical, and individual variations that impact migraine development and prognosis. Results: The inclusion criteria were satisfied by 94 migraine patients in total, with a mean age of 36.9 ± 9 years and they are predominantly females 75.5%. The majority of the participants (76.6%) were on medication to relieve migraine attacks and only 13.9% reported that >75% of attacks were relieved by medication. Almost all of the patients (96.8%) used to drink coffee and tea. The prevalence of depression and migraine was revealed to be 42.6% mild and 8.5% severe among the participants. Four statistically significant correlations (p < 0.05) were young age, being female, low level of education at higher risk to have depression compared to another group of migraineurs.Conclusion: A neurological disorder that commonly causes disability is migraine. Numerous studies have shown that mood disorders and migraines are often co-occurring, and these individuals are more likely to have a migraine-related disability. This research has shown that it is beneficial to prevent psychiatric comorbidity by using PHQ-9 as a regular screening tool for migraine patients. Migraines vary from other headache types by the following symptoms: lasting four to 72 h; unilateral location; pulsing nature; moderate to severe severity; increased by physical activity; and progresses with nausea, vomiting, phonophobia, or photophobia. Aura symptoms may precede migraine headaches . MigrainThe outpatient neurology service department at King Fahd Hospital-Hofuf in AlAhsa, Saudi Arabia, was the site of the descriptive, observational, and correlational study. All patients who visited a neurology clinic from May to December 2021 and were diagnosed with a migraine headache and receiving regular follow-up care. A brief description of the study was given to the participants who had autonomy for rejection. The privacy and confidentiality of results were maintained. The criteria for inclusion were adults≥18 years of age and diagnosed with primary migraine by a physician at least 6 months ago and not having other comorbidities or psychiatric illnesses. The patients were given access to an online or paper-based questionnaire. The questionnaire was divided into three sections: the first section asked about biographical information. The second section included both conventional and alternative treatment options that individuals utilized to relieve migraine attacks. The Patient Health Questionnaire serves as the last component for the measurement of the prevalence of depression using scales that have been validated and translated (PHQ-9) into Arabic -16. The Data analysisThe data were collected, reviewed, and then fed to Statistical Package for Social Sciences version 21 . All statistical methods used were two-tailed with an alpha level of 0.05 considering significance if the p-value is less than or equal to 0.05. As for PHQ-9, the overall score was obtained by summing all discrete scores for the items which ranged from 0 to 24 points. Participants’ classification according to depression severity was applied in reference to the scale documented cut-off points. Descriptive analysis was done by prescribing frequency distribution and percentage for study variables including participants' bio-demographic data, using drugs and other methods to relieve migraine attacks, medical history, and PHQ-9 items, with depression prevalence and severity. Cross tabulation for showing the distribution of participants’ depression severity according to their bio-demographic data was carried out with the Pearson chi-square test for significance and exact probability test for small frequency distributions.A total of 94 participants fulfilling the inclusion criteria with clinically diagnosed migraine completed the study questionnaire. Participants' ages ranged from 18 to more than 45 years with a mean age of 36.9 ± 12.4 years old. Exactly 70 participants (74.5%) were females. Single participants were 19 (20.2%) while 70 (74.5%) were married. As for education, 62 (66%) participants were university graduates and 23 (24.5%) had below university level of education. Exactly 50 (53.2%) participants were not employed, 30 (31.9%) were non-healthcare workers or students and 14 (14.9%) were healthcare workers/students. A monthly income of less than 5000 SR was reported among 28 (29.8%) participants, and 30 (31.9%) had a monthly income of 5000-10000 SR. Exactly 16 (17%) participants complained of chronic health problems  participants reported using drugs to relieve migraine attacks. The attack severity was relieved by less than 25% of its severity among 24 (33.3%) of them, while 23 (31.9%) reported relief of 25%-50%, and only 10 (13.9%) were relieved by more than 75%. As for alternative methods, 33 (35.1%) reported using Islamic therapy , 30 (31.9%) used traditional medicine (herbs), and 24 (25.5%) used Cupping therapy, while 24 (25.5%) did not use any of them. Among users, attack severity was relieved by less than 25% among 34 (48.6%), while 10 (14.3%) relived by more than 75%. Smoking was reported among 10 (10.6%) participants while 91 (96.8%) had coffee and tea but soft drinks were taken among 29 (30.9%)  of the study participants with migraine had no or minimal depression, 40 (42.6%) had mild depression, 12 (12.8%) had moderate depression, 21 (22.3%) complained of moderately degree depression, and 8 (8.5%) had severe depression . Also, severe depression was detected among 34.3% of females with migraine in comparison to 20.8% of males (p=0.005). About 39.1% of participants with below university education had severe depression compared to 33.3% of those with post-graduate degree (p=0.002). Severe depression was detected among 35.7% of participants with low income compared to 11.1% of those with the highest income level (p=0.004) . Also, nearly one-third of them used herbs, Islamic therapy for relieving the pain, besides drugs. Cupping therapy was used by one-quarter of the participants, and many of them used more than one method. About half of those participants reported poor attack severity improvement with the methods used.LimitationsOur study's findings have certain limitations. First, as our data were cross-sectional, we were unable to evaluate the direction of the relationship between depression subtypes and migraine intensity. To evaluate the chronological sequence between the development of depression and migraine, longitudinal investigations are necessary. Another limitation is the relatively small number of sample size. They vary in gender proportions as the majority of the participants were females; thus, future research should include more men. There are also variances in comorbidity, disability, pain severity, and frequency of episodes. We did not make a distinction between episodic and chronic migraine, or between migraine with and without aura. Further retrospective and bidirectional research with a large sample size are recommended to investigate this disparity.The current study established that migraine headache is a significant disorder associated with a higher occurrence of psychiatric disorders, especially depression and anxiety. Drug-induced pain relief was poor and alternative methods were also used with no satisfactory relief of pain attacks. These findings can help to create awareness and encourage comprehensive synchronized methods for the management of migraine in healthcare settings. Migraine-associated depression was higher among females, youth, and low socio-economic categories.


This prospective longitudinal epidemiological study was aimed at investigating the occupational SARS-CoV-2 infection risk of long distance train services in Germany. Three different employee groups  within the workforce of the German railway carrier Deutsche Bahn Fernverkehr AG were studied based on their contact frequency with passengers and colleagues. Approximately 1100 employees were tested by PCR for acute infections and by antibody detection for past infections in June 2020, October 2020 and February 2021. Cumulative incidence (acute and past infections) after the third  test series in February 2021 was 8.5% : 8.5% (95% CI 6.2–11.2) for train attendants, 5.5% (95% CI 2.9–9.5) for train drivers and 11.8% (95% CI 7.6–17.2) for maintenance workers. Between June 2020 and October 2020, the incidence was 1.2% (95% CI 0.6–2.3): 1.2% (95% CI 0.4–2.7) for train attendants, 1.1% (95% CI 0.1–3.9) for train drivers and 1.4% (95% CI 0.17–5.10) for maintenance workers. Between October 2020 and February 2021, it was 5.1% (95% CI 3.6–6.8): 5.2% (95% CI 3.3–7.8) for train attendants, 1.6% (95% CI 0.3–4.5) for train drivers and 8.8% (95% CI 4.9–14.3) for maintenance workers. Thus, contrary to expectation our exploratory data did not show train attendants to be at the highest risk of SARS-CoV-2 infections among the employee groups. In line with expectations, train drivers, representing the low contact group, seemed at lowest occupational risk. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus that causes the respiratory disease COVID-19 (coronavirus disease 2019). It first appeared in December 2019 in the metropolis of Wuhan, China and led to a pandemic within a few months. In Germany, everyday life has been affected by SARS-CoV-2 since spring 2020.The clinical course of COVID-19 is non-specific and ranges from asymptomatic, mild symptoms  to severe pneumonia with respiratory failure and death.Since asymptomatic and mild courses result in a high number of unreported cases, it is still difficult to determine the actual number of SARS-CoV-2 infections. Numerous studies therefore focus on seroprevalence, i.e. the presence of SARS-CoV-2 antibodies, to determine and follow infection rates over an extended period of time , 2.In Germany, several seroepidemiological studies were initiated after the onset of the pandemic, some of which focused on professions with infection-relevant contacts to examine the relationship between occupational contacts and infection risk. The SERODUS I and SERODUS II studies, which compared 2000 randomly selected residents with 700 employees and family members of fire crews and rescue service who were exposed to frequent occupational contacts with other people, revealed a seroprevalence of 3.1% for the general population and 4.4% for the high contact group, indicating an increased risk of SARS-CoV-2 infections for professions with high contact frequencies [Similarly, a prospective longitudinal serological survey of healthcare workers of different organisational units in the first wave of the pandemic in a quaternary care hospital in Munich also showed that increased occupational contacts with COVID-19 patients correlate with a higher seroconversion rate  [Also, a study from Columbia including 7045 workers showed that participants with multiple contacts to other people during their work shift had a higher seroprevalence for SARS-CoV-2 compared to the general population [Infection risk in public transportation was studied in China, where a positive correlation between the risk of infection, co-travel time and seat location in relation to an index patient was found. This result was based on data from a total of 2334 index patients and 72 093 close contacts with co-travel times of 0–8 h from 19 December 2019 through 6 March 2020 [In Germany in September 2020, the German railway carrier Deutsche Bahn Fernverkehr AG compared the number of PCR-confirmed SARS-CoV-2-positive cases between its employees of boarding service and non-boarding service. It was shown that boarding service staff had a slightly higher prevalence (0.31%) compared to other employees (0.26%), although the difference was within normal statistical fluctuations. Meanwhile, SARS-CoV-2 prevalence in the general population during the same period was 0.4% and thus comparable to that of the DB Fernverkehr personnel .The motivation for this study was prompted by the wish to better understand the infection dynamics and risk for staff and indirectly for travellers in long distance trains in Germany. To this end, a longitudinal design with three time points for cross-sectional data collection and analysis was chosen so that not only time-dependent prevalence data could be collected but also actual incidence rates over defined periods could be assessed. The three test series took place in June 2020, October 2020 and February 2021. While for the first two test series, the B.1 variant was predominant in Germany, during the third test series, the alpha variant (B.1.1.7) was predominant and accounted for 67.2% of cases in Germany whereas beta (B.1.351) and delta (B.1.617.2) combined accounted for 3.2% .In this multi-centre, prospective, longitudinal cohort study, the prevalence  and incidence of SARS-CoV-2 infections of three employee groups with varying frequencies of contact to passengers  were tested. Nasopharyngeal swabs were taken for PCR testing and blood samples were taken for IgG antibody testing from all participating employees at study sites in Berlin, Frankfurt, Hamburg and Munich at three points in time  separated by approximately 4 months. In addition, demographical and epidemiological data of interest with regard to risk of infection were obtained from the employees.Study sites were established in or near the central station in each respective city (in Berlin at the train station Ostbahnhof). In Hamburg, a second study site at one of the train maintenance sites was opened additionally in each test series.The study sites were selected to cover different regions of Germany .Employees were enrolled in a ratio of 8:3:3 (train attendants: train drivers: maintenance workers). At each test series, approximately 1100 employees were tested. The sample size of this longitudinal cohort study was justified by the expected precision of the estimation : upper limit–lower limit) for the seroprevalence. A seroprevalence of 1% was assumed in each employee group. The resulting width of the CI  were judged to be sufficient to gain preliminary insights in the infection status of employees of DB Fernverkehr.For each employee group and location, a randomly sorted list of employees was created and the first employees were invited by letter sent to their private address. Each letter contained an individual code that allowed employees who were interested in participating in the study to register for a test appointment. Invited employees who either did not respond or explicitly declined the invitation were replaced by inviting employees next on the list. This approach assured the best feasible approximation to a random selection of employees per employee group and location, reflecting the actual demographics of the group.In the second and third test series, participants from the previous test series were re-invited with a higher priority to obtain the necessary sample size for the longitudinal study design. Contact data were acquired again and merged by company-wide unique personnel number to (i) react to potentially changed postal addresses and (ii) exclude employees who lost their eligibility (e.g. due to retirement or a change in eligibility). Vacant slots were filled by inviting employees as per the randomised procedure described above. As a result, in the second and third test series, participants consisted of employees who already took part in the previous test series and of those who were newly recruited. No formal test was performed to compare the results of these subgroups.® GENE SARS-CoV-2 test with the analysis performed on the Roche LightCycler® 480II), whereas blood samples were taken to test for SARS-CoV-2-specifig IgG antibodies (Anti-SARS-CoV-2 ELISA (IgG) test by EUROIMMUN AG). The IgG test recognises the S1 domain of the spike protein including the receptor-binding domain, which was used as evidence of a past infection. According to the manufacturer EUROIMMUN AG , the sensitivity of the antibody test is 94.4% for samples obtained 10 days after symptom onset or after verification of a positive infection, while the specificity is 99.6% [After obtaining informed consent at each test series, nasopharyngeal swabs were taken to detect acute SARS-CoV-2 infections by PCR  and seroprevalence (SARS-CoV-2 antibodies) were calculated as the apparent prevalence (ratio of positive test results to non-missing test results per test series).The cumulative incidence was defined as the number of employees with at least one positive test result (PCR or antibody test) since their enrolment into the study. Thus, in case a subject had been tested positive, the subject was counted positive for all subsequent visits.χ2 test and descriptive P-values were provided. Employees who did not return for subsequent testing (drop-outs) were replaced. Subgroups were defined by the first enrolment to the study  to investigate the impact of replacing the lost to follow-up employees. Additionally, χ2 tests were applied to analyse potential associations  of all demographical and epidemiological characteristics (irrespective of the employee group) on the cumulative incidence. Analyses were described in a statistical analysis plan, which was finalised prior to the analysis and performed by using the statistical software SAS® version 9.4.Incidence was defined as the number of employees who had been tested negative (both PCR and antibody test) in the previous test series but positive (either PCR or antibody test) in the subsequent test series. Additionally, 95% Clopper–Pearson CI were calculated for each employee group and overall. Possible differences between the employee groups were tested by using a vs. 31%), the average age was 45 years, the prevalence of cardiovascular disease was 9.7% and of diabetes was 3.6%, and 28% have smoked in the past 12 months , followed by train drivers (11.1%) and train attendants (6.9%). Furthermore, train drivers had the highest rate of non-smokers (86.3%) as compared to maintenance workers (75.8%) and train attendants (65.3%) . Complete data on baseline characteristics are compiled in Supplementary material 01 (Tables S10–17).P = 0.1155) .Data on acute infections are summarised in P = 0.9908) .At the second test series, out of 1078 tested employees, three train attendants, one train driver and one maintenance worker were tested positive by PCR. One of the three train attendants tested positive was aware of his infection and thus had been isolated. This employee was also tested antibody-positive. Unlike the other four employees who were tested positive and were asymptomatic, he also reported symptoms. Based on these data, the overall acute prevalence across the three employee groups was 0.5% (95% CI 0.2–1.2). Stratified by employee groups, it was 0.5% (95% CI 0.0–1.4) for train attendants, 0.4% (95% CI 0.0–2.3) for train drivers and 0.4% (95% CI 0.0–2.4) for maintenance workers (P = 0.6252) .At the third test series, out of 1035 tested employees, two train attendants and one maintenance worker had a positive PCR test. Two of the three PCR-positive employees (both train attendants) were aware of their infection before the time of testing, because they already had a positive PCR test result, which was performed outside this study several weeks before the third test series and had already completed the isolation period. These two employees also had positive antibody findings. The PCR-positive maintenance worker, on the other hand, reported having had mild symptoms of common cold a few days before the testing. At the time of testing, this employee was asymptomatic. The antibody result was negative, probably due to the short time period between the infection and the testing. The overall acute prevalence across the three employee groups was 0.3% (95% CI 0.1–0.8). Stratified by employee groups, it was 0.3% (95% CI 0.0–1.2) for train attendants, 0.0% (95% CI 0.0–1.6) for train drivers and 0.5% (95% CI 0.0–2.5) for maintenance workers (P = 0.2198).Seroprevalence data are summarised in P = 0.7160) .At the second test series, 26 out of 1076 employees were tested positive, including 16 train attendants, four train drivers and six maintenance workers. Thus, the overall seroprevalence was 2.4% (95% CI 1.6–3.5) across the three employee groups. Stratified by employee groups, seroprevalence was 2.6% (95% CI 1.5–4.2) for train attendants, 1.7% (95% CI 0.5–4.3) for train drivers and 2.6% (95% CI 1.0–5.7) for maintenance workers (P = 0.1390).At the third test series, out of 1014 tested employees, 66 were tested positive, including 39 train attendants, nine train drivers and 18 maintenance workers. Thus, the overall seroprevalence was 6.5% (95% CI 5.1–8.2) across the three employee groups. Stratified by employee groups, seroprevalence was 6.8% (95% CI 4.9–9.2) for train attendants, 4.0% (95% CI 1.8–7.4) for train drivers and 8.5% (95% CI 5.1–13.1) for maintenance workers  to 38.5% (second test series) .Out of 944 participants with non-missing values in the third test series for the calculation of the cumulative incidence over the entire study, 80 were tested either PCR- or antibody-positive at least once since enrolment into the study. These included 45 train attendants, 12 train drivers and 23 maintenance workers. Cumulative incidence (acute and past infections) after the third  test series in February 2021 was therefore 8.5% : 8.5% (95% CI 6.2–11.2) for train attendants, 5.5% (95% CI 2.9–9.5) for train drivers and 11.8% (95% CI 7.6–17.2) for maintenance workers .Incidence data are summarised in Out of 773 participants who were tested negative during the second test series and attended the third test series, 39 employees were tested positive by antibody or PCR in the third test series. This corresponded to an incidence of 5.1% (95% CI 3.6–6.8) for the period between the second (26 October 2020 to 30 October 2020) and the third test series (24 February 2021 to 2 March 2021). Of these 39 employees, 22 were train attendants, three were train drivers and 14 were maintenance workers resulting in an incidence of 5.20% (95% CI 3.3–7.8), 1.6% (95% CI 0.3–4.5) and 8.8% (95% CI 4.9–14.3), respectively .We have analysed factors that are commonly associated with infection risk in order to understand whether observed differences between the employee groups can be explained by differences in these associated risk factors. An association between past symptoms – especially fever , rhinitis , coughing , headache , anosmia and ageusia  – and cumulative incidence was found, which varied across test series. In the initial testing rounds, we found elevated infection rates in staff with diabetes and in households with children . In general, private habits, e.g. meeting with more people during free time , and individual health status, such as cardiovascular disease , had an This longitudinal study compared the prevalence and incidence of SARS-CoV-2 infections between three employee groups of DB Fernverkehr AG  to estimate the occupational risk of infection. The employee groups were selected based on their differing contact exposure with passengers and colleagues. Underlying the primary objective of obtaining seroprevalences from the different employee groups was the question on whether the different contact frequencies of the employee groups had an impact on the infection risk. The study also allowed to determine cumulative incidences over a period of almost one year. This study was explorative in nature and did not strive for a formal hypothesis testing on the differences in employee group infection risks. Throughout the three test series, acute prevalence of SARS-CoV-2 remained relatively low across all three employee groups ranging from 0.1% to 0.5%. The differences observed between employee groups were in all three test series not meaningful due to the low number of positive test results. A steady increase in seroprevalence was observed during the course of the study, reflecting the ongoing pandemic. While in the first test series it was 1.9%, it increased to 2.4% in the second test series and to 6.5% in the third test series. The observed differences among the employee groups were marginal. Maintenance workers exhibited the relatively highest seroprevalence throughout all three test series. The steady increase in seroprevalence in the course of the study was partly a consequence of the long half-life of SARS-CoV-2 IgG antibodies  could not be considered in the analysis.Second, the study did not account for a possible underestimation of the prevalence of acute infections at each test series. This bias would be introduced by employees not attending study visits because of acute symptomatic infections or being quarantined.Third, it should be noted that although hygiene rules such as wearing masks applied in general in the same way for all three employee groups, the degree of social contact during work was different among these groups. Masks were also mandatory for passengers during their journey . Train aFourth, the estimation of the nationwide infection rate is also subject to several caveats. For example, the testing strategy in Germany underwent a change, which initially was more restricted due to limited capacity than later in the pandemic, possibly leading to an over- or underestimation of the true number of infections in Germany at the time of the test series in this study. In addition, no statistical test was performed to identify any differences in population characteristics between the employees of Deutsche Bahn Fernverkehr and the general population, such as age and gender distribution limiting the extrapolation of the results to the general population.Fifth, the study does not allow direct conclusions for the infection risks of passengers, since this was not examined. However, since train attendants and passengers share the same compartment, it can be assumed that the infection risk for passengers emanating from train attendants is modest as well.Also, it is noted that detection of reinfections is limited by the chosen study design and definition of incidence. A person tested positive in two consecutive test series would only have been counted once.In summary, the results of this study did not show any evidence that train attendants with the highest degree of contacts to passengers and colleagues had noticeably higher rates of SARS-CoV-2 infections than train drivers and maintenance workers. Maintenance workers exhibited the highest seroprevalence followed by train attendants and train drivers. The overall infection rates within the tested employees of the DB Fernverkehr were also in accordance with the nationwide infection dynamics. However, in general, no conclusive differences between the employee groups were observed either in acute prevalence or seroprevalence throughout the study. Nonetheless, the incidence between the second and the third test series showed a marked difference between the employee groups. The maintenance workers markedly showed the highest incidence, followed by train attendants and train drivers.


Caffeine acts as a competing antagonist of adenosine receptors, increasing the release of norepinephrine and the activation of noradrenergic neurons. Long-standing schizophrenia patients frequently develop a comorbidly high daily caffeine intake. This could be explained by its relationship with smoking .To determine caffeine consumption in schizophrenia and predisposing factors.Cross-sectional study designed on a sample of 68 outpatients with a follow-up of at least 5 years at the Mental Health Unit, aged between 18 and 65 years, diagnosed with schizophrenia (ICD-10). Average daily caffeine intake was quantified by reference values for each beverage: coffee (66.7mg/100ml), tea (30mg/100ml), soft or energy drinks (11.5mg/100ml). High intake was defined as a consumption of ≥200mg of caffeine per day. Retrospective review of medical records revealed tobacco use and negative symptoms observed on the PANSS scale. Statistical analysis were performed using SPSS v21.0 (significance p<0.05).88.2% of the subjects were daily caffeine consumers with a mean intake of 146.7mg/day (SD=5.8), and a mean consumption time of 6.2 years. Coffee was the predominant beverage in 66.7% of the cases, followed by soft or energy drinks (25%) and tea (0.1%). 45% of participants also had a high caffeine intake of ≥200 mg/day. Comorbid smoking was found in 93% of these patients. Negative symptomatology prevailed among caffeine consumers (PANSS-N= 41.3).Xanthine abuse seems to be highly prevalent in people with schizophrenia, and there may be a relationship with smoking and negative psychotic symptoms.No significant relationships.


Ureteroscopy is a major diagnostic and therapeutic technique for lesions of the ureter and intrarenal collecting system.A retrospective chart review was done at St. Paul's Hospital Millennium Medical College, Ethiopia to determine the outcome of ureteroscopy and factors affecting it. The study period was from January 2018 to April 2018. Multivariate analysis was done to determine factors affecting stone clearance and success rate.One hundred six patients who underwent semirigid ureteroscopy were included in the study. The male-to-female ratio was 1.8:1. The mean age of the patients was 36.4 years (±12.6). Ninety-six (90.6%) patients were found to have ureteric stones, while 9(8.5%) patients had a ureteric stricture. Ureteroscopy therapeutic interventions for stones were successful in 89 (92.7%) patients. The mean procedure time and postoperative hospital stay were 44 minutes (±23.7) and 2.5 days (±2.5) respectively. Intraoperative complications  occurred in 6(5.7%) patients. The stone clearance rate was 54.7% (52). The site of obstruction was passed in 93 patients making the success rate of the procedure 87.7%. The absence of intraoperative complications was significantly associated with success rate. Patients with intraoperative complications have low success rate (20%) compared to patients without complications (92.3%), p=0.42.Semirigid ureteroscopy had a good success rate, especially for stones in the distal ureter and if there is no flexible ureteroscope, it is an acceptable alternative. Ureteroscopy (URS) is retrograde instrumentation that involves inserting an endoscope into the ureter and calyceal system via the lower urinary tract. Although it was first described in 1912, it was in 1977 that Goodman reported the first rigid ureteroscopy for therapeutic purposes. It gradually became a standard method for diagnosing and treating ureter and intrarenal collecting system lesions. Urolithiasis, ureteric stricture, pelvic ureteric junction (PUJ) obstruction, ablation of transitional cell carcinoma, and retrieval of migrated stones are the most common indications for ureteroscopy  filling defect greatly enhances diagnostic accuracy. It not only allows you to see the UUT, but it also allows you to biopsy any lesion you find for histopathological confirmation (Ureteroscopy (URS) has evolved from a diagnostic procedure with limited visualization to an accurate surgical intervention allowing access to the entire urinary system since its first description over 30 years ago. However, as URS has become more popular, it has resulted in several incidents or complications, as well as new prevention strategies. Minor complications such as colic, fever, and hematuria to major complications such as ureteric perforation and avulsion may occur as a result of URS .Although St. Paul's Hospital Millennium Medical College (SPHMMC) is one of the two leading referral hospitals in the capital, the endo-urology unit has not more than 2 years of experience in URS and uses a semirigid ureteroscope. The stones are fragmented with a pneumatic lithotripter. To the authors' knowledge, there is no similar study conducted at SPHMMC and there is only one study in the country. This study helps to know the outcome of URS and to suggest plans that improve it. The objective of the study was to determine the outcome of URS and the factors affecting it.A retrospective chart review was done at SPHMMC, Addis Ababa, Ethiopia. St. Paul's Hospital Millennium Medical College is a tertiary teaching hospital with 110 surgical beds. Department of Urology has 21 beds and one daycare endo urologic unit. Five senior urologists are working in the department and teach both undergraduate medical students and post-graduate urology and general surgery residents. All patients who underwent ureteroscopy from February 1, 2017, to January 31, 2018, G.C were included in the study. Patients who have undergone ureteroscopy in other healthcare facilities and were referred for repeated ureteroscopy, self-discharged patients, and patients with incomplete charts were omitted from the study.The operating theatre logbook was used to identify patients and each patient's medical records and imaging were examined to extract the data. Urology residents who took training, collected data on patients' sociodemographic characteristics, diagnosis, site, and size of stones, complications, and stone clearance rate using a pretested data collection format. Data collection was monitored and data quality was verified daily. The data was analyzed using SPSS version 23. Binary logistic regression was used to determine the influence of various factors on stone clearance and success rate. Variables with p-values of < 0.3 during a bivariate analysis were further subjected to a multivariate analysis and considered significant at p-values < 0.05. Minor complications of ureteroscopy like fever and colic are not documented and is a limitation of the study.This study was done based on the Helsinki declaration. An ethical approval letter was obtained from the SPHMMC Institutional Review Committee. Since the study is retrospective, the committee approved us to proceed without patient consent. The data collected was used solely for the study and patient information remained confidential.In this study, stone clearance is when a patient has no residual stone in the ureter on imagining studies (KUB or non-contrast CT scan) during the first 6 months of follow-up after ureteroscopy. A successful procedure is when the ureteric obstruction is passed either with a double J stent or a ureteroscope.Ureteroscopy was done for 115 patients during the study period. Nine patients were not included in the study because of incomplete data and lost charts, making the response rate 92.2%. Among the 106 patients, 68 (64.2%) were males and 38 (35.8%) were females with a 1.8:1 male to female ratio. The mean and median age of the patients were 36.4 years (±12.6) and 36.5 years (13–73 years) respectively. Most patients, 63 (59.4%), come from an urban area. Almost all, 104 (98.1%), patients were admitted as elective. Spinal anesthesia was used for 55(51.9%) patients, in the remaining 51(48.1%) patients the procedure was done under general anesthesia.During ureteroscopy, 96 (90.6%) patients were found to have ureteric stones, while 9(8.5%) patients had a ureteric stricture and one patient had a normal ureteroscopy finding. Among the patients who had ureteric stones, 44 (45.8%) patients had left side stones and 45 (46.9%) patients had right ureteric stones. Seven (7.3%) patients had bilateral stones. Out of the 96 patients diagnosed with ureteric stone, the site of the stone was mentioned in 92 patients. Stones were found at the distal ureter in 38 (41.3%) patients, at the mid ureter in 13 (14.1%) patients, and in the proximal ureter in 41 (44.6%) patients. Among the 73 patients for whom the size of the stone was described, it was < 1 cm in 32 (43.8%) patients, 1–2 cm in 38 (52.1%) patients, and 2–3 cm in 3 (4.1%) patients. Thirty-seven (38.5%) patients who had ureteric stones had concomitant renal stones.Ureteroscopy therapeutic interventions for stones were successful in 89 (92.7%) patients. For 36 (37.5%) patients only a double J stent was inserted, for 10 (10.4%) patients complete stone extraction was done, and for 41(42.7%) patients pneumonic or lesser stone fragmentation was done, in 2 (2.1%) patients the stone was dislodged proximally. In the remaining 7 (7.3%) patients with stone, ureteroscopy was only diagnostic, all therapeutic interventions were not successful . For allOut of the total 106 patients, a ureteric stent was inserted for 91(85.8%) patients, but for the remaining 15(14.2%) patients (1 stricture and 14 stone patients) it was not inserted. In patients with ureteric stones, the stent was inserted only for 82(85.4%) patients. The mean and median procedure times were 44 minutes (±23.7) and 40 minutes (10–120), respectively. The mean and median postoperative hospital stay was 2.5 days (±2.5) and 1 day (1–13).Major intraoperative complications were documented in 6(5.7%) patients, all with ureteric stones. Ureteric avulsion occurred in 1 (0.9%) patient. Hemorrhage and Ureteral perforation occurred in 2 (1.9%) and 3 (2.8%) patients, respectively. The ureteric avulsions occurred during basket stone extraction. The patient was managed with Ureteroneocystostomy with Boary's flap. All perforations were associated with impaction of stone. One perforation was reconstructed by open procedure and for 2 of the perforations, URS was postponed, and repeat URS was successful. For both patients with gross hemorrhage, repeat URS was done some other time and was successful. All ureter perforations and hemorrhages occurred in patients with proximal ureter stones (p=0.006). No association was found between the size of the stone and complications (p=0.74). All above complications occurred in patients for whom stone crushing and JJ stent insertion was tried/done (p=0.4). The mean procedure time and postoperative hospital stay were 90 minutes (±50.6) and 5.7 days (±7.8) respectively, in patients with complications. This is nearly two times lower in patients without complications (2 days and 38.5 minutes).Out of the 106 patients, 55(51.9%) patients were discharged improved without any other interventions. For 25 (23.6%) patients repeat URS was done. Eleven (10.4%) patients underwent ESWL, open surgical procedure was done for 10(9.4%) patients (3 were ureteric stricture). Three (2.8%) patients were referred for PCNL and for 2(1.9%) patients' other procedures were done.Except one, all patients with ureteric stones had postoperative follow-up imaging. On postoperative imaging, stone was not visualized in 52 patients making the stone clearance rate 54.7%. In the remaining 43(45.3%) patients, the postoperative image showed remaining stones. Only 4(44.4%) patients with ureteric stricture had documented postoperative imaging, which showed normal position of the stent.In both bivariate and multivariate analysis, the postoperative stone clearance rate was significantly associated with a distal ureteric location of stones . Patients with bilateral stones (28.6%), mid (46.2%) and proximal (43.9%) ureter stones, and large-sized (>1cm) stones had the lowest stone clearance rate even though it was not statistically significant . The sitOn bivariate analysis, the presence of associated renal stone (p=0.001), proximal ureter location of the stones (p≤0.001), and the absence of intraoperative complications (p=0.002) were associated with success rate. However, on multivariate analysis, only the absence of intraoperative complications was significantly associated with success rate  .In this study, there was a male predominance 1.8 times) and the mean age of the patients was 36.4 years (±12.6). Other studies conducted in India, Ethiopia, and Egypt had also comparable findings  patients. For 36 37.5%) patients only double J stent was inserted, for 10 10.4%) patients complete stone extraction was done and for 41(42.7%) patients stone fragmentation was done, in 2 (2.1%) patients the stone was dislodged proximally. In the remaining 7 patients with stones, the ureteroscopy was only diagnostic. However, the study from Ethiopia by D. Andualem et. al found complete stone extraction for 19 (50%) patients. Nine (23.7%) patients had only double J stenting while no therapeutic ureteroscopy procedure was done for 6 (15.8%) patients. For 2 (5.3%) patients the stone was crushed and in 2 (5.3%) others the stone was dislodged  ,4. This Patients with bilateral stones, mid and proximal ureter stones, and large-sized (>1cm) stones had the lowest stone clearance rate. In both bivariate and multivariate analyses, the postoperative stone clearance rate was significantly associated with a distal ureteric location of stones. Similarly, the study conducted by Subhani GM et.al. found a low success rate for proximal ureter and >1 cm sized stones . Other sOut of the 106 patients, 55(51.9%) patients were discharged improved without any other interventions. For 25 (23.6%) patients repeat URS was done, 11(10.4%) and 3(2.8%) patients were referred for ESWL and PCNL respectively, an open surgical procedure was done for 10(9.4%) patients and 2(1.9%) patients underwent other procedures. It is slightly different from a paper done in Ethiopia by D. Andualem et.al, of the 38 stone patients, 24 (63.2%) were discharged after ureteroscopy while 12 (31.5%) patients had to undergo other procedures and for 2 (5.3%) patients repeat ureteroscopy was done (


Facebook use among Teenagers has become a very common phenomenon. Its use can resuly in Facebook addiction .To estimate the prevalence of problematic Facebook use among a sample of school-going adolescents.This is a cross-sectional and descriptive study carried out among 110 school-going adolescenthe at 2 state colleges in Sidi Bouzid. We used a pre-established self-questionnaire containing 2 parts: a part exploring the socio-demographic data of the adolescent and a psychometric part: Bergen Facebook addiction Scale.Study participants had a mean age of 14.4 years with extremes of 12 to 17 years. The sex ratio (M / F) (46/64) of the participants was 0.71.In our population, 13 students (11.8%) were smokers. Two students (1.8%) consumed alcohol. Cannabis use was noted in only one student.The majority of students (102), or 92.7%, had been online for more than a year.The daily Facebook connection time was more than 4 hours for 20.9%. Boredom was the number one reason for logging into Facebook for 82 students (74.5%) followed by curiosity for 45 students (40.9%). Fifteen students (13.6%) were addicted to Facebook (score> 10 on the Bergen Addiction Scale.Facebook can be a useful and interesting tool to maintain and develop a network of relationships and create new ones. Its problematic use or addiction to Facebook has become a new scourge of public health. Faced with the negative impact of this addiction, It would be necessary to rationalize this use.No significant relationships.


To compare the efficacy of letrozole (LTZ) vs clomiphene citrate (CC) for ovulation induction in patients having polycystic ovarian syndrome (PCOS).This randomized controlled trial was conducted at The Department of Obstetrics & Gynecology, Nishtar Medical University Hospital, Multan, Pakistan from January 2021 to June 2021. A total of 78 women aged 18 to 30 years, diagnosed having PCOS were enrolled. In Group-A, 39 women were given LTZ, 5mg for five days of menstrual cycle. In Group-B, 39 women were given CC, 100mg for five days of menstrual cycle. All patients underwent transvaginal scan (TVS) for the evaluation of efficacy in terms of ovulation induction.2. Overall, mean duration of infertility was found to be 2.62±0.74 years. Among 70 patients who completed the follow ups and analyzed regarding efficacy, in Group-A, efficacy was noted in 23 (59.0%) patients in comparison to 14 (35.9%) in Group-B (p=0.0413). Mean endometrial thickness was significantly better in Group-A versus Group-B .Overall mean age was noted to be 25.41±2.84 years. Most of the patients, 51 (65.4%) belonged to rural area of residence. There were 52 (66.7%) patients with BMI less than 25 kg/mAiming ovulation induction, letrozole in comparison to clomiphene citrate was found to have significantly better efficacy among women having anovulatory PCOS. Polycystic ovarian syndrome (PCOS) is known to be a frequent endocrine disorder and considered to a common cause of infertility, depressive symptoms and life dissatisfaction.6Various strategies are adopted for the induction of ovulation like weight reduction, metformin and laparascopic ovarian drilling. The most popular treatment options for infertility among with PCOS is through medications like gonadotrophins, pituitary follicular stimulating hormone therapies and aromatase inhibitors.9Letrozole (LTZ) is an aromatase inhibitor and in comparison to CC, LTZ is linked with better thickening of endometrium and pregnancy rates while congenital anomalies are comparable between the two drugs.The objective of this study was to compare the efficacy of LTZ vs CC for ovulation induction in women having PCOS.www.ClinicalTrials.gov as “NCT05075863”. Sample size of 78 (39 in each group) women was estimated considering 95% confidence interval, 80% power of test and presumed efficacy of LTZ and CC as 63.3% and 29.4% respectively.10This randomized controlled trial was conducted in the “Department of Obstetrics & Gynecology, Nishtar Medical University Hospital, Multan, Pakistan” from January 2021 to June 2021 after the approval from “Institutional Ethical Committee” . Informed consent was sought from participants of this study. This trial was registered at A total of 78 women aged 18 to 30 years with PCOS presenting in outpatient department (OPD) of Obstetrics & Gynecology, Nishtar University Hospital, Multan” were included. Diagnosis of PCOS was made as existence of any two of these: peripherally arranged 2-9 follicles of 8-10mm, increased LH and FSH ratio above two, history of oligomenorrhea (less than 6 cycles / years) or serum testosterone above 0.65 ng/ml.Women with thyroid disorders as shown in TSH between 0.5 to 5 IU/L, T3 between 4.3 to 8.6 Pmol/l and T4 between 9 to 22 mol/l or those with hyperprolactinemia (serum prolactin above 400 miu/l) were excluded. Women having duration of infertility above five years, or infertility in the partner, malignancy involving the breast or ovary were also no included.th day on TVS and/or small/collapsed on 16th day on TVS, ovulation induction was considered yes or otherwise. Endometrial thickness was also evaluated. A special proforma was designed to record all study data.Detailed demographic history including name, age, body mass index (BMI), duration of infertility and area of residence were recorded. All women were allocated randomly to two groups through computer generated numbers . Women iSPSS version 26.0 was used for data analysis. Qualitative data like area of residence and efficacy were presented by frequency and percentages. The quantitative data like age, duration of infertility, BMI and endometrial thickness were presented as mean±SD. Post stratification chi-square was applied. Independent sample t-test was used to compare endometrial thickness. P value < 0.05 was considered significant.2) was noted to be 23.74±2.96 while there were 52 (66.7%) patients with BMI less than 25 kg/m2. Overall, mean duration of infertility was found to be 2.62±0.74 years. Comparison of characteristics of study participants in between both study groups are shown in Overall mean age was noted to be 25.41±2.84 years while 70 (89.7%) patients were aged between 21 to 30 years. Most of the patients, 51 (65.4%) belonged to rural area of residence. Overall, mean BMI (kg/mThere were eight women who were lost to follow up (3 in Group-A and 5 in Group-B) so 70 patients were included in the final analysis (36 in Group-A and 34 in Group-B). Distribution of efficacy among patients of both study groups is shown in Mean endometrial thickness was noted to be 8.1±1.5 mm in Group-A in comparison to 6.8±1.9 mm in Group-B while the difference turned to be statistically significant (p=0.0022).st choice of treatment for women having PCOS. CC is known to reduce uterine receptivity which could be a reason that it results in reducing the likelihoods of conception. Few of the major drawbacks of clomiphene citrate include poor efficacy rates (around 22% of livebirths), high chances of multiple pregnancy (3-8%).14For some decades, clomiphene citrate has been considered as the 1th day of menstrual cycle in 35.9% patients who used CC in comparison to 59.0% patients in LTZ group (p=0.0413). A study evaluating use of CC up to a period of six months noted 25% failure of ovulation induction while live birth rate was 22.5%. It has been stated that CC results in ovulation inductions rates between 50-85% but the conception rates are not very high (15-27%).8In the present study, it was noted that following five days of treatment in both study groups, ovulation induction occurred on 14ery high -27%.15-1As this was a single center study with a relatively small sample size, the results cannot be generalized. As we noted efficacy in both treatment groups as per defined criteria, we did not record antral follicle count which would have given us further insight about these drugs. We noted ovulation induction and we did not plan to analyze live-birth of pregnancy outcomes. More prospective trials having randomized nature and involving larger sample size will further confirm the findings of this study.Aiming ovulation induction, letrozole was found to have significantly better ovulatory efficacy in comparison to clomiphene citrate among women having PCOS.


Although left and right displacement of the abomasum and abomasal volvulus are well-known disorders of cattle, a comparative evaluation of the clinical, laboratory and ultrasonographic findings of these types of abomasal displacements has not been undertaken. Therefore, the objective of this study was to compare these conditions in a large population of cows. The medical records of 1982 dairy cows with left displaced abomasum , right displaced absomasum  and abomasal volvulus  were searched for the results of clinical, laboratory and ultrasonographic evaluations.The main clinical findings were an abnormal demeanour in 48.2% of the cows, reduced rumen motility in 89.7% and decreased intestinal motility in 61.1%. Ballottement and simultaneous auscultation and percussion and simultaneous auscultation were positive on the left side in 96.9% of the cows with LDA and on the right in 98.5% of the cows with RDA and in 99.3% of the cows with AV. Ultrasonography was useful for diagnosing LDA in 97.9% of the cows and RDA/AV in 90.2% of the cows. The laboratory findings characteristic of abomasal reflux syndrome varied in severity; 83% of the cows had hypokalaemia, 67% had increased rumen chloride concentration, 67% had an increased base excess and 50% had haemoconcentration. Based on the clinical signs, a definitive diagnosis was made in 75.0% of the cows with LDA and in 22.5% of the cows with RDA/AV. Ultrasonography was required for a definitive diagnosis in another 22.0% of the cows with LDA and in 53.0% of the cows with RDA/AV. Laparotomy or postmortem examination was required for reliable differentiation of RDA and AV.LDA, RDA and AV differ with respect to the severity and the frequency of several abnormal clinical, laboratory and ultrasonographic findings as well as the methods required for a diagnosis. The clinical and laboratory findings in cows with left (LDA) and right displaced abomasum (RDA) and abomasal volvulus (AV) have been described in textbooks –4, revieTransrectal abdominal exploration of a cow with LDA may show medial displacement of the rumen , 4, 9 orUltrasonographic examination of cows with LDA from the left side shows that the abomasum is located between the abdominal wall and rumen –22, 33. Although LDA, RDA and AV are well-known disorders of cattle, a comparative evaluation of the clinical, laboratory and ultrasonographic findings of these types of abomasal displacements has not been undertaken. Therefore, the objective of this study was to compare these findings in a large population of cows. A secondary goal was to determine the proportion of cases in which the definitive diagnosis was achieved using the results of clinical examination, ultrasonography or exploratory surgery.From a dissertation that comprised 2043 data sets , 61 recositus inversus )was calculated [Each cow was assigned to either the LDA, RDA or AV group. The clinical, laboratory and ultrasonographic variables were analysed for all cows combined and for each type of displacement separately. The data were compiled using FileMaker Pro Advanced 13.0  and analysed with IBMegative;).1 A trueThe Shapiro–Wilk and Kolmogorov–Smirnov tests showed that all numerical variables had a non-normal distribution.The demeanour was mildly abnormal in 51.2% of the cows, moderately abnormal in 43.6% and severely abnormal in 4.6% , sawhorseDistention of the left flank was obvious in 21.0% of the cows with LDA, and distention of the right flank occurred in 17.2% of cows with AV and 8.9% of cows with RDA (P < 0.05). Cows with RDA or AV had abdominal enlargement more often than cows with LDA (3.6 and 7.9% vs. 1.1%) (P < 0.01). A papple-shaped abdomenThe heart rate  ranged from 36 to 160 bpm, and cows with AV had a higher heart rate than cows with LDA and RDA (91 vs. 84 bpm) (P < 0.01)  ranged from 12 to 120 breaths per min with a mean of 30 breaths per min. It was within the reference interval (15 to 25 breaths per min) in 44.8% of all cows, decreased (12 to 14 breaths per min) in 1.7% and increased (26 to 120 breaths per min) in 53.5%. The respiratory rate did not differ significantly among the three groups.The rectal temperature ranged from 36.1 to 41.8 °C and was within the reference interval (38.5 to 38.9 °C) in 32.0% of all cows, decreased (36.1 to 38.4 °C) in 19.3% and increased (39.0–41.8 °C) in 48.6%. A decreased rectal temperature was more common in cows with RDA and AV than in cows with LDA (23.5% and 31.3% vs. 15.6%) (P < 0.01). The correlation coefficients r for heart and respiratory rates and rectal temperature ranged from 0.11 to 0.34 (P < 0.01) .Rumen contractions were reduced or absent in 89.7% of all cows Table . Cows wiOf the foreign body tests, positive results were seen with the back grip in 10.5% of cows, the pole test in 8.1% and percussion of the reticular area in 1.1%; a positive back grip test was more common in cows with RDA than in cows with LDA (16.1 vs. 9.2%) (P < 0.05). On the left side, BSA and/or PSA were positive in 96.9% of the cows with LDA and on the right, they were positive in 98.5% of the cows with RDA and in 99.3% of the cows with AV. Intestinal motility was reduced or absent in 61.1% of all cows; this finding was more common in cows with RDA and AV than in cows with LDA (77.5% and 77.8% vs. 53.1%) (P < 0.01). Compared with healthy cows, the amount of faeces in the rectum was decreased in 51.6% of all cows, and in 9.6%, the rectum was empty. In cows with AV, the latter finding was more common than in cows with LDA and RDA (20.9% vs. 5.8% and 14.8%) (P < 0.01). Cows with no intestinal motility had an empty rectum more often than cows with reduced or normal intestinal motility (25.7% vs. 10.4% and 4.8%) (P < 0.01). Dark or black manure was more common in cows with RDA and AV than in cows with LDA (17.2% and 19.1% vs. 5.8%) (P < 0.01). Thin porridge-like faeces occurred in 17.4% of all cows, thick porridge-like faeces in 11.7% and watery faeces in 7.6%. In 24.5% of all cows, the faeces contained poorly digested plant fragments. Abnormal faecal contents included mucus (9.1%), blood (4.9%) and fibrin (1.4%); cows with RDA had mucus in the faeces more often than cows with LDA (P < 0.01), and cows with RDA and AV had blood in the faeces more often than cows with LDA (P < 0.01). The results of transrectal palpation of the abomasum also differed among the three groups; the abomasum was palpated more frequently in cows with AV than in cows with RDA and LDA (22.1% vs. 11.2% and 1.1%) (P < 0.01).A cool skin surface temperature was more common in cows with AV than in cows with RDA and LDA (57.0% vs. 44.5% and 25.7%)  (P < 0.01) (Table 2 = 38.4). Findings characteristic of LDA were seen in 97.9% of 893 cows with LDA when examined on the left side [Ultrasonography allowed correct identification of LDA significantly more often than RDA  (Table 2 = 192) and haemoconcentration (chi2 = 52): the blood urea concentration was increased in 61% of the cows with AV compared with 43% of cows with RDA and 21% of cows with LDA (P < 0.01) ; the cows with LDA had the highest mean concentration (43 mmol/L) and the cows with AV had the lowest Table . As a re2) Table  and rume; the cowOf all laboratory variables, only the activities of GLDH  and SDH  had diagnostic sensitivities > 90%  had at least one comorbidity; 624 (31.5%) had one, 589 (29.8%) had two, 326 (16.5%) had three and 190 (9.6%) had more than three. The most common comorbidity was ketosis  followed by mastitis , metritis/endometritis  and hepatic lipidosis . Other accompanying diseases included gastrointestinal parasitism , abomasal ulcer , claw disorders , bronchopneumonia , fascioliasis  and caecal dilatation .The clinical findings did not differ significantly between cows without and with one, two, three or more than three comorbidities. This applied to the mean respiratory and heart rates, rectal temperature and to the frequency distributions of all variables listed in Tables Laboratory variables did not differ significantly between cows with one and no concomitant diseases Table . Cows wi2 = 286)  of 1341 cows with LDA and in 144 (22.5%) of 641 cows with RDA/AV  and 4.4 times more common than AV (67.6 vs. 15.3%). This distribution was similar to previously reported ratios of LDA to RDA of 4:1  and 4.7:A moderately to severely abnormal demeanour occurred significantly more often in cows with AV 75.9%) than in cows with RDA (58.6%) or LDA (39.4%). Interestingly, other authors observed considerably fewer cows with LDA (7.4%)  and RDA 5.9% thanRumen motility was reduced in 45.5% of all cows and absent in another 44.2%; rumen atony is always a serious clinical sign. Other authors described the rumen motility of cows with LDA as normal or reduced and only rarely as absent , 2. A poSimilar to rumen atony, intestinal atony is always a serious clinical sign and it was not surprising that this was significantly more common in cows with AV (20.2%) and RDA 15.3%) than in cows with LDA (4.2%). The higher incidence of intestinal atony in cows with AV was why no faeces were found in the rectum of 20.9% of those cows. This was significantly less common in cows with RDA 14.8%) and LDA (5.8%). Palpation of the displaced abomasum transrectally is an important finding, which was almost twice as common in cows with AV than in those with RDA (22.1 vs. 11.2%) and occurred in only 1.1% of cows with LDA. However, these frequencies are considerably lower than those reported by others for RDA (30.8%)  and AV , which was in agreement with earlier reports of haemoconcentration in cows with RDA  and AV , 49. HaeAn increase in the activities of γ-GT (61%), AST (81%), GLDH (84%) and SDH (98%) was seen in the cows with abomasal displacement. Similar findings have been reported previously , 51–53 aA definitive diagnosis of LDA could be made in 75% of all cows based on the results of clinical examination alone. In 25% of the cows, the diagnosis was uncertain because the results of BSA and/or PSA were also positive on the right side, or rumen atony was present and the results of double auscultation of the rumen could not be interpreted. An uncertain diagnosis was rarely attributable to an inexperienced clinician because supervision by an expert was standard procedure. When ultrasonographic findings were included, the diagnosis could be made in 97% of cases.The diagnostic capabilities of ultrasonography using 3.5- and 5.0 MHz linear and convex transducers did not differ from 1998 to 2016. Although the quality of ultrasonograms markedly improved in the study period, the ultrasonographic findings in cows with LDA, RDA and AV did not change. Ultrasonography provides valuable information about the position and size of the abomasum . One stuThe frequent occurrence of concomitant diseases is in agreement with the findings of other studies, which were recently discussed , 60 and The occurrence of numerous abnormal clinical and laboratory variables differed significantly in cows with LDA, RDA and AV. A clinical diagnosis based on clinical examination was possible in 75.0% of cows with LDA but in only 22.5% of cows with RDA/AV. Ultrasonography allowed a definitive diagnosis in another 53.0% of the latter, but laparotomy was required in 24.0% and postmortem examination in 0.5%. Laparotomy or postmortem examination is required for the differentiation of RDA and AV. Ultrasonography is useful to confirm a tentative diagnosis of LDA and RDA/AV. Laboratory findings have little diagnostic utility but they allow the assessment of the severity of the illness and in unclear cases may provide information about abomasal reflux syndrome. Differentiation of RDA and AV is not possible based on clinical, ultrasonographic and laboratory findings, and laparotomy or postmortem examination is required.


To evaluate the clinical value of Aldo-keto reductase family 1 member B10 (AKR1B10) in the diagnosis and prognosis of hepatocellular carcinoma (HCC).A search of the PubMed, China Biology Medicine, Cochrane, and Embase databases was performed to conduct meta-analyses to evaluate the accuracy of AKR1B10 in diagnosing HCC and to assess the impact on prognosis of patients after curative resection of HCC.A total of 12 different cohorts from 11 studies including 2747 HCC patients and 2053 controls showed that the pooled specificity and the pooled sensitivity of AKR1B10 for the diagnosis of HCC were 0.78 (95% CI: 0.69–0.85) and 0.85 (95% CI: 0.77–0.90), respectively. The pooled sensitivity and specificity of serum AKR1B10 for the diagnosis of HCC were 0.80 (95% CI: 0.70–0.86) and 0.87 (95% CI: 0.77–0.93), respectively. The pooled sensitivity and specificity of AKR1B10 in malignant tumor tissue for the diagnosis of HCC were 0.78 (95% CI: 0.61–0.89) and 0.82 (95% CI: 0.69–0.90), respectively. The pooled sensitivity and specificity of AKR1B10 to distinguish HCC from benign liver disease were 0.71 (95% CI: 0.62–0.78) and 0.84 (95% CI: 0.77–0.89), respectively. The sensitivity and specificity of AKR1B10 combined with alpha fetoprotein (AFP) in the diagnosis of HCC were 0.84 (95% CI: 0.79–0.88) and 0.88 (95% CI: 0.73–0.95), respectively. The pooled sensitivity and specificity of AKR1B10 in malignant tumor tissue for the diagnosis of early-stage HCC were 0.85 (95% CI: 0.62–0.95) and 0.88 (95% CI: 0.81–0.93), respectively. A meta-analysis of five studies including 798 patients demonstrated that high AKR1B10 expression in liver malignant tumor was associated with better overall survival in patients with HCC after hepatectomy .AKR1B10 exhibits a great clinical value in the diagnosis of HCC, especially for early-stage HCC, with excellent diagnostic accuracy. Furthermore, AKR1B10 expression can predict the prognosis of HCC patients after hepatic resection. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide –3. SinceAldo-keto reductase family 1 member B10 (AKR1B10), originally identified as a human small intestinal aldose reductase and aldose reductase-like protein, is a cytosolic NADPH-dependent reductase that catabolizes a variety of endogenous compounds, such as dicarbonyls, aromatic, aliphatic aldehydes, and certain pharmaceutical ketones. The AKR1B10 gene is located on chromosome 7q33, and the AKR1B10 protein consists of 316 amino acids . RecentlIn the current study, we aimed to evaluate the diagnostic value of AKR1B10 in serum and tumor tissue for HCC, its ability to distinguish HCC from benign liver disease, and its accuracy in diagnosing early-stage HCC. Furthermore, we aimed to explore the impact of AKR1B10 expression on the OS and recurrence-free survival (RFS) of HCC patients after hepatectomy.Literature search was performed on PubMed, China Biology Medicine, Cochrane, and Embase databases to identify studies reporting the diagnostic and prognostic value of AKR1B10 in patients with HCC. The deadline for retrieval was April 2, 2022. The search terms included in the search strategy were as follows: ((AKR1B10) OR (Aldo-keto reductase1-B10)) AND ((liver cancer) OR (hepatoma) OR (hepatic carcinoma) OR (hepatocellular carcinoma)).All studies were individually screened by the title and abstract, followed by a full-text assessment by two reviewers. Divergences were solved by discussion until consensus was reached. The inclusion criteria were as follows: (1) research population included patients with HCC and non-HCC ; (2) AKR1B10 was analyzed in all patient groups; (3) prognostic studies needed to provide sufficient data to calculate the HR and its 95% CI; (4) diagnostic studies needed to provide sufficient data to calculate sensitivity and specificity; and (5) there were no language restrictions. The exclusion criteria were as follows: (1) insufficient data provided to calculate the HR; (2) insufficient data provided to calculate the sensitivity and specificity; (3) abstracts, reviews, letters, case reports, or publications; or (4) animal or cell experiments.The data were individually extracted by two authors, following a predefined scheme. Divergences were solved by discussion until consensus was reached. Extracted study characteristics included the following: first author, publication year, type of cancer, number of patients, number of controls, type of sampling, aim of the study, and detection method of the AKR1B10 expression level. On the basis of the aim and outcome of the included studies, studies were classified into the diagnostic and prognostic groups. Studies were classified into the diagnostic group when AKR1B10 was used as a biomarker to diagnose HCC or to differentiate HCC from healthy controls. Studies were categorized into the prognostic group when the association between the high or low expression level of AKR1B10 and survival was provided.The quality of included studies was scored separately by two reviewers. Divergences were solved by discussion until consensus was reached. The quality assessment of diagnostic accuracy studies (QUADAS) criteria was used to assess the quality of studies related to the diagnosis of HCC by AKR1B10. The Newcastle Ottawa scale was used to assess the quality of studies related to the prognosis of HCC.2) was used to evaluate the degree of inter-study statistical heterogeneity. Substantial heterogeneity was indicated if I2 values were ≥ 50%, and the random-effects model was adopted [All analyses were conducted using Stata 16 and Meta-Disc 1.4 software. For diagnostic studies, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) and their 95% confidence intervals (CIs) were calculated to assess the diagnostic value of AKR1B10 for HCC. Furthermore, the Spearman correlation analysis method was used to examine threshold effect heterogeneity among diagnostic studies. For prognostic studies, the hazard ratio (HR) and its 95% CI were collected to assess the correlation between AKR1B10 expression and prognosis of HCC. If the study only provided Kaplan Meier survival curves, the Engage Digitizer version 2.11 software was used to extract the relevant values from the survival curves and calculate the HR (95% CI) , 15. The adopted . The Dee adopted .The flowsheet of the study screening process is shown in To verify whether there was heterogeneity caused by the AKR1B10 threshold among the included diagnostic studies, we used the Meta-Disc 1.4 software to perform the Spearman test to detect the threshold effect, and the correlation coefficient and P value between the sensitivity logit and the 1—specificity logit were calculated. The results showed that the Spearman correlation coefficient and P value were -0.413 and 0.183 (> 0.05), respectively, indicating that the heterogeneity caused by different AKR1B10 thresholds did not exist in the 11 diagnostic studies.A total of 11 studies –29 incluThe pooled sensitivity and specificity of AKR1B10 in discriminating HCC from non-HCC were 0.78 (95% CI: 0.69–0.85) and 0.85 (95% CI: 0.77–0.90), respectively. The PLR, NLR, DOR, and AUC with their corresponding 95% CIs were 5.3 (95% CI: 3.3–8.5), 0.26 (95% CI: 0.17–0.38), 21.00 (95% CI: 9.00–46.00), and 0.89 (95% CI: 0.86–0.91), respectively . Our metThe tested samples of AKR1B10 included serum and malignant tumor tissue. To verify whether different sources of AKR1B10 have different diagnostic accuracies for HCC, we analyzed the diagnostic accuracy of AKR1B10 levels for HCC in two samples. A total of five articles –23 incluTo verify whether AKR1B10 levels detected by different detection method have different diagnostic accuracy for HCC, a subgroup analysis was performed. ELISA was used to measure AKR1B10 expression levels in serum in four studies , 22, 23,To assess the accuracy of AKR1B10 in distinguishing HCC from benign liver diseases, such as chronic hepatitis and cirrhosis, we collected and analyzed the relevant data from five studies , 25–28 iAFP is a traditional diagnostic marker for HCC. To evaluate the diagnostic accuracy of AKR1B10 combined with AFP for HCC, a total of five articles –23 incluA total of three studies –24 incluA total of five studies –34 incluTo assess the publication bias of included studies, the linear regression test of Deeks’ funnel plot asymmetry was conducted. The pooled Deeks’ test result of the diagnostic studies was p = 0.55 , which iIn HCC cells, inhibition of AKR1B10 expression resulted in cell cycle arrest and impaired cell proliferation, suggesting that AKR1B10 may exert tumorigenic effects through enhanced cell growth . UpregulIn this meta-analysis, after excluding heterogeneity due to threshold effects, we showed that the overall sensitivity and specificity of AKR1B10 for the diagnosis of HCC were 78% and 85%, respectively. Subsequently, we analyzed the main sources of heterogeneity and divided the included diagnostic studies into six subgroups. Our study showed that the sensitivity and specificity of serum and tissue as test specimens for AKR1B10 in the diagnosis of HCC were similar, which indicates that the different tested specimens were not the main source of heterogeneity. In addition, the control population was not consistent among the included studies, which may have affected the accuracy of AKR1B10 for diagnosing HCC.With the development of science and technology, simultaneous determination of AKR1B10 and AFP is feasible. Our meta-analysis table indicates a higher sensitivity and specificity of AKR1B10 combined with AFP for the diagnosis of HCC compared with AKR1B10 or AFP alone. In addition, serum AFP levels have been reported to be not only associated with HCC but also to be elevated in patients with benign liver diseases, such as hepatitis and cirrhosis . Our metIt has been reported that the 5-year survival rate of patients can be improved to more than 50% if HCC can be detected at an early stage . HoweverThe main difficulty in treating HCC is the high frequency of tumor recurrence even after liver transplantation and radical resection , which cTo the best of our knowledge, no meta-analysis has yet been reported on the association between AKR1B10 expression levels and the diagnosis and prognosis of HCC. However, our study has some limitations. First, patients from different included studies had different characteristics, which are common in the evaluation of the accuracy of diagnostic tests. It may have affected the accuracy of diagnostic analysis. Second, the cut-off for AKR1B10 positivity was not uniform in the literature included in this study, which may have affected the accuracy of AKR1B10 for HCC diagnosis. Finally, most of the studies on AKR1B10 for diagnosing HCC were conducted in Asian populations, which may have resulted in a population selection bias.In conclusion, our meta-analysis suggests that AKR1B10 has a high diagnostic value for HCC and can be used as a novel screening method. Notably, AKR1B10 has excellent diagnostic efficacy for early-stage HCC and shows good performance when combined with AFP to diagnose HCC. In addition, AKR1B10 can predict OS and RFS of HCC patients after hepatectomy. However, more large cohort studies or large randomized controlled multicenter trials are needed to further explore the clinical value of AKR1B10 for patients with HCC.S1 Checklist(PDF)Click here for additional data file.


Poorer metacognitive abilities are recognized as strong predictors of social functioning deficits in individuals with schizophrenia.The aim of the current study is to examine metacognitive functioning in people with schizophrenia and to explore correlations between metacognition, symptoms and general functioning.It was a cross-sectional study involving outpatients diagnosed with schizophrenia and followed in the psychiatry “C” department at Hedi Chaker university Hospital, in Sfax -Tunisia, between may and december 2018. Sociodemographic, clinical and therapeutic data were measured using self-reported questionnaires, and metacognition was assessed with the Metacognition Assessment Scale – Abbreviated version (MAS-A). The general functioning was measured with The Global Assessment of Functioning (GAF).-3). Greater metacognition was significantly correlated with fewer negative symptoms , but metacognition was not significantly correlated with positive psychotic symptoms, cognitive disorganisation, excitement or emotional distressA total of 74 participants participated in the study. The average age was 34.1 ± 11.8 years and the sex-ratio was 1.6. The average score of global assessment of functioning was 49.39±10. Means and standard deviations on MAS scores were as follows: self-reflectivity 4.18 (1.46), understanding of others’ minds 3.20 (1.06), decentration 2.5 (1.8), mastery 2.54 (1.85), and the MAS total scores 12.42 (6.17). The results indicate that poor social functioning is associated with metacognitive difficulties (r=0.27, p<10These findings underscore the importance of interventions designed to enhance the patients’ metacognitive capacities, that is, the more proximal capacities linked to poorer social functioning.