Effectiveness of Saccharomyces Boulardii CNCM I-745 probiotic in acute inflammatory viral diarrhoea in adults: results from a single-centre randomized trial.

BACKGROUND: Probiotics are effective for treating acute infectious diarrhoea caused by bacteria, but there are inconsistent results for the effectiveness of probiotics for diarrhoea caused by viruses. In this article we want to determine whether Sb supplementation has an effect on acute inflammatory viral diarrhoea diagnosed with the multiplex panel PCR test. The aim of this study was to evaluate the efficacy of Saccharomyces boulardii (Sb) as a treatment in patients diagnosed with viral acute diarrhoea. METHODS: From February 2021 to December 2021, 46 patients with a confirmed diagnosis of viral acute diarrhoea diagnosed with the polymerase chain reaction multiplex assay were enrolled in a double-blind, randomized placebo-controlled trial. Patients received paracetamol 500 mg as a standard analgesic and 200 mg of Trimebutine as an antispasmodic treatment plus 600 mg of Sb (n = 23, 1 × 109/100 mL Colony forming unit) or a placebo (n = 23) orally once daily for eight days. The improvement in and severity of symptoms were measured using a symptom diary, the Patient Global Impression and the Patient Global Impression of Change scales (days 4 and 8), both answered and recorded by the patient. RESULTS: Of the 46 patients who completed treatment, 24 (52%) were men and 22 (48%) were women. The average age was 35.6 ± 12.28 years (range 18 to 61 years). The average duration of the evolution of illness at the time of diagnosis was 0.85 ± 0.73 days (maximum 2 days). On day 4 after the diagnosis, 20% reported pain and 2% reported fever, but on day 8, no patient reported pain or fever. On day 4, 70% of patients in the Sb group and 26% in the placebo group reported improvement (P = 0.03), based on the Patients' Global Impression of Change scale, which assesses patient's rating of overall improvement. These findings suggest that 3 to 4 days of treatment with Sb helped to improve symptoms of diarrhoea caused by a virus. CONCLUSION: Treatment with Sb on acute inflammatory diarrhoea of viral aetiology shows no changes regarding the severity of the symptoms; nevertheless, it seems to impact improvement positively. TRIAL REGISTRATION: 22CEI00320171130 dated on 16/12/2020, NCT05226052 dated on 07/02/2022.

Comparison of Central Aortic Pressure between Women with Preeclampsia and Normotensive Postpartum Women from an Urban Region of Western Mexico.

Background and Objectives: Central aortic pressure (CAP) can be measured through noninvasive methods, and CAP wave analysis can provide information about arterial stiffness. The objective of this study was to compare CAP in women with preeclampsia and normotensive postpartum women from an urban region in western Mexico. Materials and Methods: We recruited 78 women in immediate puerperium, including 39 with preeclampsia and 39 with normotension, who received delivery care in our hospital between September 2017 and January 2018. Pulse wave analysis was used to assess central hemodynamics as well as arterial stiffness with an oscillometric device. For this purpose, the measurement of the wave of the left radial artery was obtained with a wrist applanation tonometer and the ascending aortic pressure wave was generated using the accompanying software (V 1.1, Omron, Japan). Additionally, the systolic CAP, diastolic pressure, pulse pressure, heart rate, and rise rate adjusted for a heart rate of 75 bpm were determined. The radial pulse wave was calibrated using the diastolic and mean arterial pressures obtained from the left brachial artery. For all the statistical analyses, we considered p < 0.05 to be significant. Results: The results were as follows: a systolic CAP of 125.40 (SD 15.46) vs. 112.10 (SD 10.12) with p < 0.0001 for women with and without preeclampsia, respectively. Systolic CAP was significantly elevated in women with preeclampsia and could indicate an elevated risk of cardiovascular disease. Conclusion: CAP is an important parameter that can be measured in this group of patients and is significantly elevated in women with postpartum preeclampsia, even when the brachial blood pressure is normal.

Clinical and Biochemical Profile Associated with Renal Recovery after Acute Kidney Injury in A Mexican Population: Retrospective Cohort Study.

Background and Objectives: Our primary objective was to study the clinical and biochemical characteristics associated with acute kidney injury (AKI) remission in a group of Mexican patients. Materials and methods: We retrospectively enrolled 75 patients who were diagnosed with AKI and separated the sample into two groups: nonremitting patients (n = 27, 36%) vs. remitting patients (n = 48, 64%). Results: We found significant relationships between nonremitting AKI and previous diagnosis of chronic kidney disease (p = 0.009), higher serum creatinine (Cr) at admission (p < 0.0001), lower estimated glomerular filtration rate (eGFR) (p < 0.0001), maximum serum creatinine during hospitalization (p < 0.0001), higher fractional excretion of sodium (FENa) (p < 0.0003) and 24-h urine protein (p = 0.005), higher serum potassium on admission (p = 0.025), abnormal levels of procalcitonin (p = 0.006), and increased risk of death (p = 0.015). Conclusion: Chronic kidney disease (CKD), lower eGFR, higher levels of serum creatinine during hospitalization, higher FENa and 24-h urine protein, abnormal levels of procalcitonin, and higher serum potassium on admission were associated with nonremitting AKI. These findings may facilitate the rapid identification of patients at risk for nonremitting AKI based on clinical and biochemical characteristics. Furthermore, these findings may inform the design of timely strategies for the vigilance, prevention, and treatment of AKI.

Evaluation of the Effects of Atorvastatin and N-Acetyl Cysteine on Platelet Counts in Patients with Primary Immune Thrombocytopenia: An Exploratory Clinical Trial.

Objective: We aimed to evaluate the efficacy of the combination of atorvastatin and N-acetyl cysteine in increasing platelet counts in patients with immune thrombocytopenia who were resistant to steroid therapy or had a relapse after treatment. Material and Methods: The patients included in this study received oral treatment of atorvastatin at a dose of 40 mg daily and N-acetyl cysteine at a dose of 400 mg every 8 h. The desired treatment duration was 12 months, but we included patients who completed at least 1 month of treatment in the analysis. The platelet counts were measured prior to the administration of the study treatment and in the first, third, sixth, and twelfth months of treatment (if available). A p value < 0.05 was considered statistically significant. Results: We included 15 patients who met our inclusion criteria. For the total treatment duration, the global response was 60% (nine patients); eight patients (53.3%) had a complete response and one patient (6.7%) had a partial response. Six patients (40%) were considered as having undergone treatment failure. Of the responder group, five patients maintained a complete response after treatment (55.5%), three patients maintained a partial response (33.3%), and one patient (11.1%) lost their response to the treatment. All of the patients in the responder group had significant increases in their platelet counts after treatment (p < 0.05). Conclusion: This study provides evidence of a possible treatment option for patients with primary immune thrombocytopenia. However, further studies are needed.

Breastfeeding Practices and Postpartum Depression in Mexican Women during the COVID-19 Pandemic: A Cross-Sectional Study.

Background: Breastfeeding is a characteristic process of mammals that ensures delivery of an adequate nutritional supply to infants. It is the gold standard food source during an infant's first months of life. Since the onset of the COVID-19 pandemic in 2020, people in quarantine have experienced a wide range of feelings, which may make isolation challenging in terms of maternal health. This study focused on the prevalence of breastfeeding practices and postpartum depression (PPD) among Mexican women during the COVID-19 pandemic. Materials and Methods: This cross-sectional study included 586 postpartum women who completed an online survey 4-8 weeks after delivery from April to December 2020 in Guadalajara, Mexico. The aim was to identify potentially depressed mothers according to the Edinburgh Postnatal Depression Scale (EPDS) and describe their breastfeeding practices. Results: The mean maternal age was 30.4 ± 4.6 years, the mean EPDS score was 9.6 ± 5.0, and the PPD prevalence according EPDS scores was 27.1%. Exclusive breastfeeding (EBF) was reported by 32.3% of mothers in the first 48 h and by 70.3% of mothers 48 h after delivery. EBF was associated with a lower prevalence of PPD during the first 48 h (p = 0.015) and after the first 48 h (p = 0.001) after delivery. Skin-to-skin contact (SSC) was reported by 385 (65.7%) mothers. PPD was less frequent in mothers practicing SSC (20.3%) than it was in those not practicing SSC (40.3%) (p = 0.001). A higher percentage of mothers practiced SSC breastfed (66.9%) and used EBF (150, 79.4%) (p = 0.012 and 0.001, respectively). Conclusions: Results suggest that the pandemic emergency and restrictions imposed on the population significantly affected the well-being of mothers after birth, and that these effects may have posed risks to the mental health and emotional stability of postpartum mothers. Therefore, encouraging BF or EBF and SSC may improve or limit depressive symptoms in postpartum mothers.

Treatment of melasma with platelet-rich plasma: A self-controlled clinical trial.

Melasma is a common circumscribed hypermelanosis of sun-exposed areas of the skin. Platelet-Rich Plasma therapy has been evidenced to inhibit melanin synthesis in animals and humans. To determine the effectiveness of platelet-rich plasma as a treatment for melasma. Twenty female patient with melasma were involved in this study. The intervention included three Platelet-Rich Plasma application sessions at 15-day intervals. Patients were evaluated before and after treatment. Variables measured included the facial melanin concentration using the melasma area and severity index score, melasma quality of life scale satisfaction grade, and histologic changes. Mean age was 41 ± 7 years. An initial MELASQOL score of 42 ± 14.8 and final score of 16.6 ± 7.2 (p = 0.008) were reported; the initial and final MASI score were 15.5 ± 8.4 and 9.5 ± 7.2 (p = 0.001), respectively. The dermatoscopy examination revealed a decrease in pigmentation after intervention (p = 0.001). Histopathologic improvement was detected in reductions in cutaneous atrophy (14 [70%] vs. 11 [55%]), solar elastosis (15 [75%] vs.11 [55%]), and inflammatory infiltrate (9 [45%] vs. 6 [30%]), before and after treatment, respectively. The intervention was associated with decreased intensity of the melasma patch and improved skin quality, shown by the MELASQOL and MASI scores.

Differences in Postoperative Pain, Nausea, and Vomiting After Elective Laparoscopic Cholecystectomy in Premenopausal and Postmenopausal Mexican Women.

BACKGROUND: Postoperative symptoms and pain after laparoscopic cholecystectomy (LC) are common in women. However, there is no evidence of differences in incidence and severity among different age groups. We evaluated whether adverse postoperative symptoms were more common in younger than in older women after LC. METHODS: One hundred and fifty premenopausal (mean age 37.6 ± 3.6 y) and 145 postmenopausal women (59 ± 5.2 y) were included in this retrospective cohort study. Clinical and anthropometric parameters were analyzed. Study endpoints were the incidences of postoperative nausea and vomiting (PONV) and pain, and the additional analgesics and antiemetics needed after surgery. RESULTS: Body mass index was normal in 42.7% of patients in the younger group and 64.8% in the older group (P < 0.001). Reported pain was more frequent and intense in the younger group throughout the study period (P < 0.01). Additional narcotics were required in 18% of premenopausal versus 7.6% of postmenopausal women (P = 0.001), and the doses used to reduce pain were higher for premenopausal women (P = 0.02). PONV was more frequent in the younger group at 1 and 6 h after surgery (P < 0.005). Rescue antiemetics were required in 29 premenopausal and 13 postmenopausal women (P = 0.01). Hospital stay was shorter for the older patients (P = 0.01). Minor morbidity was observed in both groups (0.7% and 2.1%). There was no mortality. CONCLUSIONS: Early PONV and pain after LC were more frequent in premenopausal women, who also required more rescue analgesic and antiemetic medication.

Anxiety and COVID-19: Coronavirus Anxiety Scale scores in medical and non-medical personnel in urban hospitals in Guadalajara. A cross-sectional survey study.

The world is facing the worst health crisis in modern history. In addition to general concerns about the effects of COVID-19 on health, hospital personnel are developing numerous mental health conditions. This cross-sectional survey study evaluated the prevalence and severity of anxiety caused by the COVID-19 pandemic using the Coronavirus Anxiety Scale (CAS) in 2136 hospital employees. For the employees who presented scores ranging from 1-20 (n = 1090, 51%), the CAS mean score was 4.22 (SD = 3.95). The mean score was higher in women than men. By work category, non-clinical hospital personnel presented the highest CAS scores.

Covid-19 en receptores de trasplante de médula ósea.

No disponible.

Gender Differences in Postoperative Pain, Nausea and Vomiting After Elective Laparoscopic Cholecystectomy.

BACKGROUND: Although reports suggest that pain and postoperative nausea and vomiting (PONV) may be more frequent in women, the evidence is inconsistent. The objective of this study was to investigate whether women are more sensitive to pain and PONV after laparoscopic cholecystectomy (LC). METHODS: A total of 370 women and 275 men were included in a retrospective cohort study. All underwent LC under standardized general anesthesia. The variables analyzed included clinical and anthropometric parameters. End points were the incidence of nausea, vomiting, pain, and the requirement for additional pain relievers and antiemetics to control these. RESULTS: The women were younger and had lower body weight than the men (p < 0.001). Body mass index was within the normal range for 50% of women and 30% of men (p < 0.001). Pain was more common in women at 1, 6, 12 and 24 h after surgery (p < 0.02). Narcotics in addition to the doses used to lessen pain intensity (p = 0.01) were required in 60 women and 19 men (p < 0.001). PONV was more frequent in women at 1 and 6 h after surgery (p < 0.01). Rescue antiemetics were required in 35 women and 11 men (p = 0.008). Hospital stay was shorter for men (p < 0.001). Four patients in each group developed postoperative complications (p = 0.14). There was no mortality. CONCLUSIONS: Early postoperative pain, nausea and vomiting after LC were more common in women, who more frequently required analgesic and antiemetic rescue medication.

[Wilkie's syndrome caused by exogenous hyperthyroidism in a patient with primary autoimmune hypothyroidism: a case report and literature review]. / Síndrome de Wilkie secundario a hipertiroidismo exógeno en una paciente con hipotiroidismo primario autoinmune: reporte de un caso y revisión de la literatura.

Wilkie's syndrome or superior mesenteric artery syndrome is an unusual cause of proximal intestinal obstruction, primarily attributed to recent weight loss. We report the case of a 19-year-old woman comes to our clinic and reports weight loss, abdominal pain, nausea, and vomiting. Laboratory tests revealed anemia, hypoalbuminemia, hypomagnesemia, and a suppressed thyroid stimulating hormone secondary to levothyroxine. A barium swallow test showed gastric dilatation, delayed gastric emptying and an axial computed tomography revealed an aortomesenteric angle of 11.7°. Conservative management with total parenteral and enteral nutrition was initiated, being the first-line treatment. In refractory cases surgery is a safe and effective option.

Oral acyclovir induced hypokalemia and acute tubular necrosis a case report.

BACKGROUND: Acyclovir is one of the most common prescribed antiviral drugs. Acyclovir nephrotoxicity occurs in approximately 12-48% of cases. It can present in clinical practice as acute kidney injury (AKI), crystal-induced nephropathy, acute tubulointerstitial nephritis, and rarely, as tubular dysfunction. Electrolytes abnormalities like hypokalemia, were previously described only when given intravenously. CASE PRESENTATION: A 54 year-old female presented with weakness and lower extremities paresis, nausea and vomiting after receiving oral acyclovir. Physical examination disclosed a decrease in the patellar osteotendinous reflexes (++ / ++++). Laboratory data showed a serum creatinine level of 2.1 mg/dL; serum potassium 2.1 mmol/L. Kidney biopsy was obtained; histological findings were consistent with acute tubular necrosis and acute tubulointerstitial nephritis. The patient was advised to stop the medications and to start with oral and intravenous potassium supplement, symptoms improved and continued until serum potassium levels were > 3.5 meq/L. CONCLUSIONS: The case reported in this vignette is unique since it is the first one to describe hypokalemia associated to acute tubular necrosis induced by oral acyclovir.

COVID-19 pandemic and its impact on medical interns' mental health of public and private hospitals in Guadalajara.

INTRODUCTION: Burnout syndrome is a global burden characterized by exhaustion, work detachment, and a sense of ineffectiveness. It affects millions of individuals worldwide, with a particularly high prevalence among medical students. Factors such as demanding education, exposure to suffering, and the COVID-19 pandemic have contributed to elevated stress levels. Addressing this issue is crucial due to its impact on well-being and health-care quality. MATERIALS AND METHODS: This cross-sectional survey study assessed fear of COVID-19 and burnout levels among medical student interns in hospitals in Guadalajara, Jalisco. The study used validated scales and collected data from September 2021 to September 2022. A snowball sampling method was employed and a minimum sample size of 198 participants was calculated. RESULTS: This study included 311 medical students (62.1% female and 37.9% male with a mean age of 23.51 ± 2.21 years). The majority were in their second semester of internship (60.5%) and from public hospitals (89.1%). Most students believed that the COVID-19 pandemic affected the quality of their internship (82.6%). Female students had higher personal burnout scores, while male students had higher work-related burnout scores. The mean score for fear of COVID-19 was 13.71 ± 6.28, with higher scores among women (p = 0.004) and those from public hospitals (p = 0.009). A positive weak correlation was found between COVID-19 scores and burnout subscales. CONCLUSION: Our study emphasizes the significant impact of various factors on burnout levels among medical students and health-care professionals during the COVID-19 pandemic. Prolonged exposure to COVID-19 patients, reduced staffing, and increased workload contributed to burnout, affecting well-being and quality of care. Targeted interventions and resilience-building strategies are needed to mitigate burnout and promote well-being in health-care settings.

A Multidisciplinary Approach to the Classification and Management of Intestinal Failure: Knowledge in Progress.

Intestinal failure (IF) is a debilitating condition characterized by the insufficient function of the gastrointestinal tract to absorb nutrients and fluids essential for life. This review consolidates recent advancements and challenges in managing IF among adult and pediatric populations, highlighting differences in etiology, management, and outcomes. Over the recent years, significant strides have been made in the nutritional and medical management of IF, significantly reducing mortality rates and improving the quality of life for patients. Key advancements include the development and availability of glucagon-like peptide-2 (GLP-2) analogs, improved formulations of parenteral nutrition, and the establishment of specialized interdisciplinary centers. Short bowel syndrome (SBS) remains the predominant cause of IF globally. The pediatric segment is increasingly surviving into adulthood, presenting unique long-term management challenges that differ from adult-onset IF. These include the need for tailored nutritional support, management of IF-associated liver disease, and addressing growth and neurodevelopmental outcomes. The therapeutic landscape for IF continues to evolve with the development of new treatment modalities and better understanding of the condition's pathophysiology. However, disparities in treatment outcomes between children and adults suggest the need for age-specific management strategies. This review underscores the importance of a nuanced approach to IF, incorporating advancements in medical science with a deep understanding of the distinct needs.

Acute Myocardial Injury Assessed by High-Sensitivity Cardiac Troponin I Levels in Adult Patients with Early Sepsis at a Tertiary Referral Center in Mexico: An Exploratory Study.

The objective of the study was to describe the frequency of acute myocardial injury (AMI) assessed by high-sensitivity cardiac troponin I (hs-cTnI) levels and to determine the possible initial risk factors (related to the characteristics of the patient, the disease, and the initial management) in a population of adult patients with early sepsis (within the first 72 h of diagnosis) in a single tertiary hospital center in western Mexico. For the inferential statistics, the proportions of the categorical dichotomous variables were compared using the chi-square test. In all analyses, p values less than 0.05 with a 95% confidence interval were considered significant. We included a total of 64 patients diagnosed with early sepsis, of whom 46 presented elevated hs-cTnI and were classified as having AMI. In our study, the frequency of AMI in patients with early sepsis was 71.87%, and no significant differences were found in all of the characteristics of patients with early sepsis with and without AMI, nor was any significant association found with any of the variables analyzed. In the population of western Mexico, the frequency of AMI in patients with early sepsis, assessed by hs-cTnI levels, is high and similar to that reported in other populations worldwide.

3D printed ventilation tubes and their effect on biological models.

BACKGROUND: Acute otitis media (AOM) causes inflammation and hearing loss. Ventilation tubes are key in treatment. 3D printing improves prostheses in otorhinolaryngology, offering precision and greater adaptability. MATERIALS AND METHODS: An experimental study was conducted with Wistar rats from July to December 2020. 3D tympanostomy tube models were designed, with technical specifications and tests performed on inexpensive 3D printers. The tympanostomy tube was inserted endoscopically. RESULTS: Procedures were performed on five rats with implants in both ears. Pre-intervention pathologies, such as atical retraction and glue ear, were found. The PLA-printed tympanostomy tube showed improvement after adjustments. Histopathological results revealed significant middle and inner ear damage. CONCLUSION: In our study, the design and 3D printing of implants fulfilled the desired functions when modified, with a height of 5 mm. Complications included PLA degradation and ear damage. There were no adverse events during observation, highlighting the need for further research on 3D-printed implants.

Risk Factors and Prevalence Associated With Conversion of Laparoscopic Cholecystectomy to Open Cholecystectomy: A Tertiary Care Hospital Experience in Western Mexico.

Introduction Laparoscopic cholecystectomy (LC) is a common procedure used for the treatment of different pathologies caused by gallstones in the gallbladder, and one of the most common indications is acute cholecystitis. The definitive treatment for acute cholecystitis is surgery, and LC is the gold standard. Nevertheless, transoperative complications (like intraoperative bleeding, anatomical abnormalities of the gallbladder, etc.) of LC and some other preoperative factors (like dilatation of bile duct, increased gallbladder wall thickness, etc.) can cause or be a risk factor for conversion to open cholecystectomy (OC). The objective of this study was to determine the risk factors and prevalence associated with the conversion from LC to OC in patients with gallbladder pathology and the indication for LC. Materials and methods This was a prospective cohort study. We included patients of both sexes over 18 years of age with gallbladder disease. To determine the risk factors associated with conversion, we performed a bivariate analysis and then a multivariate analysis. Results The rate of conversion to OC was 4.54%. The preoperative factors associated with conversion, in the bivariate analysis, were common bile duct dilatation (p=0.008), emergency surgery (p=0.014), and smoking (p=0.001); the associated intraoperative variables were: laparoscopic surgery duration (p <0.0001), Calot triangle edema (p=0.033), incapacity to hold the gallbladder with atraumatic laparoscopic tweezers (p=0.036), and choledocholithiasis (p=0.042). Laparoscopic Surgery duration was the only factor with a significant association in the multivariate analysis (p=0.0036); we performed a receiver operating characteristic (ROC) curve analysis and found a cut-off point of 120 minutes for the duration of laparoscopic surgery with a sensitivity and a specificity of 67 and 88%, respectively. Conclusion The prevalence of conversion from LC to OC is similar to that reported in the international literature. The risk factors associated with conversion to OC, in this study, should be confirmed in future clinical studies, in this same population, with a larger sample size.

Diagnostic Efficacy of Chest Computed Tomography with a Dual-Reviewer Approach in Patients Diagnosed with Pneumonia Secondary to Severe Acute Respiratory Syndrome Coronavirus 2.

To compare the diagnostic effectiveness of chest computed tomography (CT) utilizing a single- versus a dual-reviewer approach in patients with pneumonia secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we conducted a retrospective observational study of data from a cross-section of 4809 patients with probable SARS-CoV-2 from March to November 2020. All patients had a CT radiological report and reverse-transcription polymerase chain reaction (PCR) results. A dual-reviewer approach was applied to two groups while conducting a comparative examination of the data. Reviewer 1 reported 108 patients negative and 374 patients positive for coronavirus disease 2019 (COVID-19) in group A, and 266 negative and 142 positive in group B. Reviewer 2 reported 150 patients negative and 332 patients positive for COVID-19 in group A, and 277 negative and 131 positive in group B. The consensus result reported 87 patients negative and 395 positive for COVID-19 in group A and 274 negative and 134 positive in group B. These findings suggest that a dual-reviewer approach improves chest CT diagnosis compared to a conventional single-reviewer approach.

Pneumocystis jirovecii Colonization in Mexican Patients with Chronic Obstructive Pulmonary Disease.

The prevalence of colonization by Pneumocystis jirovecii (P. jirovecii) has not been studied in Mexico. We aimed to determine the prevalence of colonization by P. jirovecii using molecular detection in a population of Mexican patients with chronic obstructive pulmonary disease (COPD) and describe their clinical and sociodemographic profiles. We enrolled patients discharged from our hospital diagnosed with COPD and without pneumonia (n = 15). The primary outcome of this study was P. jirovecii colonization at the time of discharge, as detected by nested polymerase chain reaction (PCR) of oropharyngeal wash samples. The calculated prevalence of colonization for our study group was 26.66%. There were no statistically significant differences between COPD patients with and without colonization in our groups. Colonization of P. jirovecii in patients with COPD is frequent in the Mexican population; the clinical significance, if any, remains to be determined. Oropharyngeal wash and nested PCR are excellent cost-effective options to simplify sample collection and detection in developing countries and can be used for further studies.