Genetic variations and phylogenetic relationship of genus Uromastyx from Punjab Pakistan / Variações genéticas e relação filgenética do gênero Uromastyx de Punjab, Paquistão

Abstract During the present study, specimens were collected from selected sites of Cholistan desert and Kalabagh Game Reserve, Punjab province, Pakistan. Each captured specimen was tagged with voucher number and morphometric measurements were taken. The average snout to vent length was 172.559±1.40 mm and average weight was 92.1±1.30 g. The DNA of Uromastyx hardwickii was amplified and sequenced using 16S rRNA primer set. The obtained DNA sequence has shown reliable and clear species identification. After trimming ambiguous bases, the obtained 16S rRNA fragment was 520 bp while 16S rRNA fragments aligned with closely matched sequence from NCBI comprised of 510 bp. Closely matched sequences of genus Uromastyx were retrieved from NCBI in blast searches. Neighbour-joining tree of genus Uromastyx was constructed based on p-distance using MEGA X. The mean intraspecific variation was 0.095±0.01 while intraspecific variation was ranging from 0-1%. Similarly, interspecific variation of Uromastyx hardwikii with Saara asmussi, Uromastyx alfredschmidti, Uromastyx geyri, Uromastyx thomasi, Uromastyx alfredschmidti was 0-12%, 0-19%, 0-19%, 0-20%, 12-19% respectively. The newly produced DNA was submitted to NCBI and accession number was obtained (MW052563.1). Results of current study provided information about the molecular and morphological identification of Genus Uromastyx. In our recommendation, comprehensive molecular based identification of Pakistan's reptiles is required to report any new or subspecies from country.

Resumo Durante o presente estudo, os espécimes foram coletados em locais selecionados do deserto do Cholistan e da Reserva de Caça de Kalabagh, província de Punjab, Paquistão. Cada espécime capturado foi etiquetado com o número do comprovante e medidas morfométricas foram realizadas. O comprimento médio do focinho à cloaca foi de 172,559 ± 1,40 mm, e o peso médio foi de 92,1 ± 1,30 g. O DNA de Uromastyx hardwickii foi amplificado e sequenciado usando o conjunto de primer 16S rRNA. A sequência de DNA obtida mostrou identificação de espécies confiável e clara. Após o corte de bases ambíguas, o fragmento de rRNA 16S obtido tinha 520 pb, enquanto os fragmentos de rRNA 16S alinhados com a sequência próxima do NCBI composta por 510 pb. Sequências semelhantes do gênero Uromastyx foram recuperadas do NCBI em pesquisas de explosão. A árvore de união de vizinhos do gênero Uromastyx foi construída com base na distância-p usando MEGA X. A variação intraespecífica média foi de 0,095 ± 0,01, enquanto a variação intraespecífica foi de 0-1%. Da mesma forma, a variação interespecífica de Uromastyx hardwikii com Saara asmussi, Uromastyx alfredschmidti, Uromastyx geyri, Uromastyx thomasi, Uromastyx alfredschmidti foi de 0-12%, 0-19%, 0-19%, 0-20%, 12-19%, respectivamente. O DNA recém-produzido foi submetido ao NCBI e o número de acesso foi obtido (MW052563.1). Os resultados do estudo atual forneceram informações sobre a identificação molecular e morfológica do Gênero Uromastyx. Em nossa recomendação, a identificação de base molecular abrangente de répteis do Paquistão é necessária para relatar qualquer nova ou subespécie do país.

Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.

A Unilateral, Pruritic Papular Eruption Following Primigravida Pregnancy.

Linear lichen planus (LLP), also known as blaschkolinear or blaschkoid lichen planus, is a rare subtype of lichen planus that presents along the lines of Blaschko. While LLP has been associated with vaccinations, neoplasms, medications, and successive pregnancies, we present a case of LLP following a primary pregnancy. A 29-year-old G1P1 female presented to dermatology for the evaluation of an intensely pruritic, whorled rash confined to her left lower leg that appeared shortly after the birth of her first child. A biopsy of the lesion and subsequent histopathology confirmed the diagnosis of LLP. The patient was treated with topical steroids with minimal response to therapy and declined further treatment.

Dissecting knowledge, guessing, and blunder in multiple choice assessments.

Multiple choice results are inherently probabilistic outcomes, as correct responses reflect a combination of knowledge and guessing, while incorrect responses additionally reflect blunder, a confidently committed mistake. To objectively resolve knowledge from responses in an MC test structure, we evaluated probabilistic models that explicitly account for guessing, knowledge and blunder using eight assessments (>9,000 responses) from an undergraduate biotechnology curriculum. A Bayesian implementation of the models, aimed at assessing their robustness to prior beliefs in examinee knowledge, showed that explicit estimators of knowledge are markedly sensitive to prior beliefs with scores as sole input. To overcome this limitation, we examined self-ranked confidence as a proxy knowledge indicator. For our test set, three levels of confidence resolved test performance. Responses rated as least confident were correct more frequently than expected from random selection, reflecting partial knowledge, but were balanced by blunder among the most confident responses. By translating evidence-based guessing and blunder rates to pass marks that statistically qualify a desired level of examinee knowledge, our approach finds practical utility in test analysis and design.

Repeat breeding: prevalence and potential causes in dairy cows at different milk pocket areas of Bangladesh.

The objective of this study was to figure out the prevalence and probable causes of repeat breeding (RB) in dairy cows. Hence, a cross-sectional study was conducted on randomly selected 265 dairy farms in Sirajganj, Bogura, Rangpur, Satkhira, and Munshiganj districts of Bangladesh from December 2018 to February 2019. Data were collected through a direct interview method using a survey questionnaire. The reproductive organs of repeat breeder cows were examined for pathological, infectious, and functional reasons, and genital tract abnormalities. Additionally, the influence of nutrition, season, and age on the frequency of RB was recorded. The prevalence of RB was 28% among the 3824 cows investigated. Among the total repeat breeder cases, 72.54% of RB cases were found in Holstein-Friesian crossbred, 23.90% in Jersey crossbred, 1.50% in Sahiwal crossbred, and 2.06% in indigenous cows. The prevalence of RB was significantly highest (P < 0.01) in Satkhira (44.35%) and lowest in the Munshiganj district (15.87%). Data indicated that a major proportion of cows significantly (P < 0.05) faced RB problems due to functional causes (34.18%), followed by pathological causes (28.01%), genital tract abnormalities (21.32%), and infectious causes (16.49%). Furthermore, the cows were remarkably (P < 0.001) affected in RB during the summer season and nutritional deficient diseases like milk fever (70%). Age (3-7 years) had a significant (P < 0.001) effect on the RB occurrence (90%) in crossbred cows. However, particular focus should be given to systematic breeding, balanced nutrition, artificial inseminator efficiency, and hygienic inseminating tools to reduce RB incidence in high-yielding crossbred cows.

Application of Artificial Intelligence in Assessing the Self-Management Practices of Patients with Type 2 Diabetes.

The use of Artificial intelligence in healthcare has evolved substantially in recent years. In medical diagnosis, Artificial intelligence algorithms are used to forecast or diagnose a variety of life-threatening illnesses, including breast cancer, diabetes, heart disease, etc. The main objective of this study is to assess self-management practices among patients with type 2 diabetes in rural areas of Pakistan using Artificial intelligence and machine learning algorithms. Of particular note is the assessment of the factors associated with poor self-management activities, such as non-adhering to medications, poor eating habits, lack of physical activities, and poor glycemic control (HbA1c %). The sample of 200 participants was purposefully recruited from the medical clinics in rural areas of Pakistan. The artificial neural network algorithm and logistic regression classification algorithms were used to assess diabetes self-management activities. The diabetes dataset was split 80:20 between training and testing; 80% (160) instances were used for training purposes and 20% (40) instances were used for testing purposes, while the algorithms' overall performance was measured using a confusion matrix. The current study found that self-management efforts and glycemic control were poor among diabetes patients in rural areas of Pakistan. The logistic regression model performance was evaluated based on the confusion matrix. The accuracy of the training set was 98%, while the test set's accuracy was 97.5%; each set had a recall rate of 79% and 75%, respectively. The output of the confusion matrix showed that only 11 out of 200 patients were correctly assessed/classified as meeting diabetes self-management targets based on the values of HbA1c < 7%. We added a wide range of neurons (32 to 128) in the hidden layers to train the artificial neural network models. The results showed that the model with three hidden layers and Adam's optimisation function achieved 98% accuracy on the validation set. This study has assessed the factors associated with poor self-management activities among patients with type 2 diabetes in rural areas of Pakistan. The use of a wide range of neurons in the hidden layers to train the artificial neural network models improved outcomes, confirming the model's effectiveness and efficiency in assessing diabetes self-management activities from the required data attributes.

A comprehensive photovoltaic study on tungsten disulfide (WS2) buffer layer based CdTe solar cell.

Transition metal di-chalcogenides (TMCDs)-Tungsten disulfide (WS2) exhibit excellent optoelectronic properties such as suitable bandgap, high absorption coefficient, good conductivity, high carrier mobility, etc. to be used as a photovoltaic material for thin-film solar cells. In the present work, we have replaced the traditional buffer CdS and ITO/ZnO window layer in CdTe solar cells with the non-toxic, earth-abundant WS2 buffer and SnO2 window layer, respectively. The SCAPS-1D solar simulator is used to investigate the potentiality of WS2 as buffer material in CdTe solar cells. This numerical study provides a comparison of the performances between the proposed structure: SnO2/WS2/CdTe/Au and the baseline structure: ITO/ZnO/CdS/CdTe/Au. The impacts of the charge carrier generation rate, spectral response, current-voltage characteristics, bulk defect density, defect density at buffer/absorber interface, operating temperature, and capacitance-voltage characteristics on the solar cell performance parameters have also been analyzed. The tolerance level of defect density in WS2 bulk and WS2/CdTe interface are found to be 1017 cm-3 and 1012 cm-3, respectively. The temperature study reveals the poor structural robustness and thermal stability of the proposed cell. The conversion efficiency of the proposed cell has found to be 20.55% at the optimized device structure. Nevertheles, these findings may provide an insight to fabricate viable, environment friendly, and inexpensive CdTe thin-film solar cells.

Abdominal Sacrohysteropexy using Proline mesh versus Mersilene tape in apical prolapse: A randomized clinical trial.

IMPORTANCE: uterine preservation is increasingly a common demand in surgical management of pelvic organ prolapse. Using Proline mesh in surgical repair of prolapse may have negative drawbacks. OBJECTIVE: compare between using Polyproline mesh and Mersilene tape in abdominal Sacrohysteropexy repairing apical prolapse stage ӀӀ or more. STUDY DESIGN: This RCT study was conducted at the Department of Obstetrics and Gynecology (Menoufia and Ain Shams university hospitals, Egypt). Eligible population included women planned Sacrohysteropexy for uterine prolapse ≥ stage 2 assigned to two groups: Mesh group (n = 38), underwent Sacrohysteropexy with polyproline mesh, and Tape group (n = 38), underwent Sacrohysteropexy using Mersilene tape. RESULTS: High statistically significant difference between TAPE group and MESH group concerning hysteropexy time was 50.4 min in TAPE group vs 90.6 min in MESH group (p < 0.001), need for post operative analgesia was14 in TAPE group vs 27 in MESH group (p < 0.005). The mean hospital stay was 2.8 days in TAPE group vs 5.2days in MESH group (p < 0.001). CONCLUSIONS: Using Mersilene tape in Sacrohysteropexy is a safe alternative to Polyproline Mesh with comparable efficacy with less complications. Tape is easier as it needs less dissection area for sacral fixation so less injury incidence.

Spiny keratoderma: A review of case reports and histopathological descriptions.

Spiny keratoderma (SpK) is a rare skin condition characterized by spine-like papules on the palms and soles. The condition is identified under several names such as "music box spine keratosis" and "palmoplantar filiform hyperkeratosis," creating ambiguity in the diagnostic and histopathologic features of the disease. In this study, we reviewed 84 cases of SpK to examine patient demographics, medical history, clinical and histopathological descriptions, and sporadic versus hereditary onset. Notably, the most used histopathological terms were "parakeratosis" and "hypogranulosis," and the most used clinical terms were "spine" and "hyperpigmented." The average age at presentation was 60.1 years with the majority of cases in males. Only 29.8% of cases were associated with a family history of SpK and underlying malignancies were present in 28.6% of cases. This review investigates the frequency of histopathologic and clinical terms used to describe SpK to provide insight into the clinical and histopathological characteristics of this rarely reported condition.

Occurrence of ticks and tick-borne mixed parasitic microbiota in cross-bred cattle in District Lahore, Pakistan.

The present study was focused on the incidence of ticks and tick-borne diseases (TTBD) in cross-bred cattle (Friesian x Sahiwal) of two farms (n = 2548) in district Lahore, Pakistan. We collected total of 572 ticks (adults and nymphs) and blood samples (10 ml) for microscopic i.e., blood smear test - Giemsa Stain (BST) and molecular analysis; Reverse Line Blot-General Primer-PCR (RLB-PCR) and Specie Specific Primer PCR (SP-PCR) from infested cattle (n = 100) from months of April to September. Results: The tick specie identified was Rhipicephalus microplus at both farms, with significant difference in infestations rate amongst both farms (p< 0.0001). The cross-bred cattle having higher ratio of Friesian blood and lower ratio of Sahiwal blood were mostly infested by ticks (p < 0.0458) and haemoparasites (p <0.474) and vice versa. The SP-PCR showed higher number of haemoparasites infection than BST, which revealed 16% T. annulata (p < 0.0001 and k value 0.485, 0.0001), 51% B. bigemina (p < 0.0001 and k value 0.485, 0.0001) and 15% A. marginale (p < 0.001 and k value 0.207, 0.001), respectively. The single infection with B. bigemina was 34% (n = 34/100) and A. marginale 6% (n = 6/100). The double infection with T. annulata/B. bigemina was 8% (n = 8/100) and B. bigemina/A. marginale 1% (n = 1/100). Whereas the triple infection with T. annulata/B. bigemina/A .marginale was 8% (n = 8/100). The phylogenetic study of isolated sequence of T. annulata revealed close homology to isolates from Iran (87%), B. bigemina to isolates from Cuba (94 to 100%) and A. marginale with isolates from Pakistan (99 to 98%).

Fly ash geopolymer as a coating material for controlled-release fertilizer based on granulated urea.

Nitrogen loss from urea fertiliser due to its high solubility characteristics has led to the invention of controlled release urea (CRU). Majority of existing CRU coatings are produced from a non-biodegradable, toxic and expensive synthetic polymers. This study determines the feasibility of fly ash-based geopolymer as a coating material for urea fertilizer. The effects of fly ash particle size (15.2 µm, 12.0 µm, and 8.6 µm) and solid to liquid (S : L) ratio (3 : 1, 2.8 : 1, 2.6 : 1, 2.4 : 1 and 2.2 : 1) on the geopolymer coating, the characterization such as FTIR analysis, XRD analysis, surface area and pore size analysis, setting time analysis, coating thickness, and crushing strength, and the release kinetics of geopolymer coated urea in water and soil were determined. Lower S : L ratio was beneficial in terms of workability, but it had an adverse impact on geopolymer properties where it increased porosity and decreased mechanical strength to an undesirable level for the CRU application. Geopolymer coated urea prepared from the finest fly ash fraction and lowest S : L ratio demonstrated high mechanical strength and slower urea release profile. Complete urea release was obtained in 132 minutes in water and 15 days in soil from geopolymer-coated urea whereas for uncoated urea it took only 20 minutes in water and 3 days in soil. Thus, geopolymer can potentially be used as a coating material for urea fertilizer to replace commonly used expensive and biodegradable polymer-based coatings.

Prevalence of intestinal nematodes infection in school children of urban areas of district Lower Dir, Pakistan.

Intestinal parasitism is the main cause of disease all over the world and described as a significant community health problem. The current study intended to find out the occurrence and identification of hazard factors linked with IPIs among 4-12 years aged shool-age children residing in Lower Dir district, Pakistan during 2019 - 2020. A cross-sectional school-based study was conducted using a pre-arranged pre-tested survey. Anthropometric data and stool collection were done to obtain the findings. The direct wet mount preparation in saline/iodine/methods was used for stool examination. Data were investigated using the GraphPad Prism 5. A total of 400 children studied (mean age of 8.6±3.6 years) the total incidence rate for the intestinal parasitic disease was established to be 71.75%. Of the 400 children studied, the overall prevalence rate for intestinal parasitic infections was found to 71.75% Ascaris lumbricoides (33.1%), Trichuris trichiura (1.04%), E. vermicularis (1.39%), Hookworm (19.86%) were identified in children living in the study area. We concluded that there is a mass scale campaigns were required to generate alertness about health and sanitation in children and the need for the development of effective poverty control programs because deworming (killing of worm with drugs) alone is not adequate to control parasitic infections.

Human health implications of trace metal contamination in topsoils and brinjal fruits harvested from a famous brinjal-producing area in Bangladesh.

A study was undertaken to determine the contents of trace metals in 60 topsoils and 80 brinjal fruits samples from a famous brinjal-producing area of Bangladesh using atomic absorption spectrophotometer. The study also looked at soil pollution levels, dietary intake of nutritionally important trace elements, and human health risks from toxic metals induced by dermal soil exposure and consumption of brinjal. The content of Pb, Ni, Cd, Cu, Fe, Mn, and Zn in brinjal fruits harvested from farmer's fields ranged from 0.204-0.729, 0.031-0.212, < 0.010-0.061, 1.819-2.668, 3.267-5.910, < 0.010-0.866 and 2.160-3.846 µg g-1, respectively, while the amount of Cr was negligible. The calculated enrichment factors showed that 70, 50, and 25% of soil sampling sites had values in the 2.00-5.00 range for Pb, Zn, and Cd, respectively, while 30% of sites had values > 5.00 for Cd, indicating moderate to significant enrichment of these metals in the soil. The study also revealed that brinjal consumption provides a tiny amount of nutritionally important trace elements required for an adult human. Regarding the computed incremental lifetime cancer risks (ILCR), the study revealed that the values for Pb and Ni in all samples and Cd in 40% of samples were several hundred times higher for males and females than the USEPA threshold level due to oral ingestion of brinjal fruits. In contrast, dermal exposures to soil trace elements were within an acceptable range. The PCA results revealed that the contents of Cd, Pb, Ni, and Cu in soils showed strong positive correlations with those elements present in brinjal. The current study suggests future traceability research, focusing on pinpointing potential entry routes for toxic elements into the vegetable food chain.

Association of Aortic Valve Sclerosis with Angiographic Severity of Coronary Artery Disease in Patients with Acute Coronary Syndrome, Aged ≤65 Years.

Aortic valve sclerosis (AVS) represents a degenerative process that progresses with advancing age. The study was intended to find out the association between aortic valve sclerosis and the severity of CAD in patient's age ≤65 years with acute coronary syndrome. This cross-sectional analytical study was carried out in the department of cardiology, National Institute of Cardiovascular Diseases (NICVD), Dhaka, Bangladesh during a period of October 2017 to September 2018. A total of 140 Acute coronary syndrome (ACS) patients undergoing coronary angiogram during index hospitalization were included in the study. Study patients were divided into two groups on the basis of echocardiographic presence or absence of Aortic valve sclerosis (AVS), with 70 patients in each group. Group I was patients with aortic valve sclerosis and Group II was patients without aortic valve sclerosis. All patients underwent transthoracic echocardiography before they underwent coronary angiography on different days. Severity of CAD was determined by Gensini score and Vessel score. Association of traditional risk factors (smoking habit, hypertension, diabetes mellitus, dyslipidaemia and family history of CAD) with severity of CAD was investigated. Coronary angiography showed that AVS group had a higher positive rate of CAD (82.9% vs. 54.3%, p<0.001) and incidence rate of triple vessel CAD (40% vs. 14.3%, p<0.001) than non-AVS group. Gensini score had higher in AVS group than non AVS group (37.9±27.8 vs. 12.5±14.2; p<0.001). Multivariate analysis showed that AVS (p=0.01) and age (p=0.04) were independent predictors of the presence of significant coronary artery disease. The study concluded that echocardiographically detected AVS is an independent predictor of coronary artery disease severity. There is positive correlation between severity of AVS and severity of CAD in patient's age ≤65 years with ACS.

Fungal conversion of chicken-feather waste into biofortified compost.

Poultry industry is amongst highly developed industries of Pakistan, fulfilling the protein demand of rapidly increasing population. On the other hand, the untreated poultry waste is causing several health and environmental problems. The current study was designed to check the potential of keratinolytic fungal species for the conversion of chicken-feather waste into biofortified compost. For the purpose, three fungal species were isolated from soil samples. These strains were pure cultured and then characterized phenotypically and genotypically. BLAST searches of 18S rDNA nucleotide sequence of the fungal isolates revealed that the two fungal isolates belonged to genus Aspergillus and one belonged to genus Chrysosporium. Optimum temperature for Aspergillus flavus, Aspergillus niger and Chrysosporium queenslandicum was 29, 26 and 25 oC, respectively. A. flavus showed maximum (53%) feather degradation, A. niger degraded feather waste up to 37%, while C. queenslandicum showed 21% keratinolytic activity on chicken feathers at their respective temperature optima. The degradation potential of these fungal species showed their ability to form compost that has agro-industrial importance.

Coonrad-Morrey total elbow arthroplasty implications in young patients with post-traumatic sequelae.

BACKGROUND: We aimed to evaluate the clinical and radiological results of total elbow arthroplasty (TEA) performed for trauma sequelae in patients <45 years of age. METHODS: This retrospective study included 63 patients aged <45 years who underwent TEA between 2005 and 2017 for previous elbow injuries. The average follow-up period was 5.23 years (range, 2-13 years). The clinical analysis included limb function according to the Mayo Elbow Performance Score, Oxford Elbow Score, and range of motion. The degree of radiolucency was determined using plain radiographic images. RESULTS: The average amplitude of elbow flexion/extension increased from 49.1 ± 36.7 to 98.7 ± 28.2 (P < .01), and the average amplitude of elbow pronation/supination increased from 87.2 ± 52.3 to 118.7 ± 26.3 (P = .02). Functional results improved from 21.4 ± 13.1 to 67.3 ± 14.5 (P < .01) on the Mayo scale, and those measured according to the Oxford scale improved from 15.4% ± 7.0% to 28.0% ± 10.6% (P < .01). Complications were observed in 16 (32.7%) patients. Among them, 10 patients (20.4%) required revision elbow arthroplasty with replacement of implant components. The overall 5-year implant survival rate was 79.4% (95% confidence interval: 63.4-91.2), and the 10-year survival rate was 77.5% (95% confidence interval: 59.3-88.2). CONCLUSION: TEA allows restoration of the full range of motion in the elbow joint and significantly improves limb function in most cases. However, the low survival rate of implants and high incidence of complications do not permit TEA to become a routine intervention for treating post-traumatic consequences in young patients.