Ethnicity-specific BRCA1, BRCA2, PALB2, and ATM pathogenic alleles in breast and ovarian cancer patients from the North Caucasus.

BACKGROUND: Mountain areas of the North Caucasus host several large ethnic communities that have preserved their national identity over the centuries. METHODS: This study involved high-grade serous ovarian cancer (HGSOC) and breast cancer (BC) patients from Dagestan (HGSOC: 37; BC: 198), Kabardino-Balkaria (HGSOC: 68; BC: 155), North Ossetia (HGSOC: 51; BC: 104), Chechnya (HGSOC: 68; BC: 79), Ingushetia (HGSOC: 19; BC: 103), Karachay-Cherkessia (HGSOC: 13; BC: 47), and several Armenian settlements (HGSOC: 16; BC: 101). The group of BC patients was enriched by young-onset and/or family history-positive and/or bilateral and/or receptor triple-negative cases. The entire coding region of BRCA1, BRCA2, PALB2, and ATM genes was analyzed by next-generation sequencing. RESULTS: A significant contribution of BRCA1/2 pathogenic variants (PVs) to HGSOC and BC development was observed across all North Caucasus regions (HGSOC: 19-39%; BC: 6-13%). Founder alleles were identified in all ethnic groups studied, e.g., BRCA1 c.3629_3630delAG in Chechens, BRCA2 c.6341delC in North Ossetians, BRCA2 c.5351dupA in Ingush, and BRCA1 c.2907_2910delTAAA in Karachays. Some BRCA1/2 alleles, particularly BRCA2 c.9895C > T, were shared by several nationalities. ATM PVs were detected in 14 patients, with c.1673delG and c.8876_8879delACTG alleles occurring twice each. PALB2 heterozygosity was observed in 5 subjects, with one variant seen in 2 unrelated women. CONCLUSION: This study adds to the evidence for the global-wide contribution of BRCA1/2 genes to HGSOC and BC morbidity, although the spectrum of their PVs is a subject of ethnicity-specific variations. The data on founder BRCA1/2 alleles may be considered when adjusting the BRCA1/2 testing procedure to the ethnic origin of patients.

Exteriorization of the uterus reduces fetoscopic cannula-induced stress and strain: A finite element model analysis.

OBJECTIVE: To estimate stresses and strains in the uterine wall and fetal membranes with single/multi-port fetoscopy, simulating either a percutaneous access or via exteriorized uterus. STUDY DESIGN: Finite element models based on anatomical dimensions, material properties and boundary conditions were created to simulate stresses, strains and displacements on the uterine wall and fetal membranes during simulated fetal surgery either via exteriorized uterus or percutaneous approach, and with one or three cannulas. Clinically, we measured the anatomical layer thickness and cannula entry point displacement in patients undergoing single port percutaneous fetoscopy. RESULTS: Simulations demonstrate that single port percutaneous fetoscopy increases stress on the fetal membranes (+105%, 128 to 262 kPa) and uterine wall (+115%, 0.89 to 1.9 kPa) compared to exteriorized uterine access. Using three ports increases stress by 110% (148 to 312 kPa) on membranes and 113% (1.08 to 2.3 kPa) on uterine wall. Finite Element Method showed 0.75 cm uterine entry point displacement from the cutaneous entry, while clinical measurements demonstrated displacement of more than double (1.69 ± 0.58 cm), suggesting modeled measurements may be underestimations. CONCLUSION: The stresses and strains on the fetal membranes and uterus are double as high when entering percutaneously than via an exteriorized uterus. Based on what can be clinically measured, this may be an underestimation.

Genome-wide superior alleles, haplotypes and candidate genes associated with tolerance on sodic-dispersive soils in wheat (Triticum aestivum L.).

KEY MESSAGE: The pleiotropic SNPs/haplotypes, overlapping genes (metal ion binding, photosynthesis), and homozygous/biallelic SNPs and transcription factors (HTH myb-type and BHLH) hold great potential for improving wheat yield potential on sodic-dispersive soils. Sodic-dispersive soils have multiple subsoil constraints including poor soil structure, alkaline pH and subsoil toxic elemental ion concentration, affecting growth and development in wheat. Tolerance is required at all developmental stages to enhance wheat yield potential on such soils. An in-depth investigation of genome-wide associations was conducted using a field phenotypic data of 206 diverse Focused Identification of Germplasm Strategy (FIGS) wheat lines for two consecutive years from different sodic and non-sodic plots and the exome targeted genotyping by sequencing (tGBS) assay. A total of 39 quantitative trait SNPs (QTSs), including 18 haplotypes were identified on chromosome 1A, 1B, 1D, 2A, 2B, 2D, 3A, 3B, 5A, 5D, 6B, 7A, 7B, 7D for yield and yield-components tolerance. Among these, three QTSs had common associations for multiple traits, indicating pleiotropism and four QTSs had close associations for multiple traits, within 32.38 Mb. The overlapping metal ion binding (Mn, Ca, Zn and Al) and photosynthesis genes and transcription factors (PHD-, Dof-, HTH myb-, BHLH-, PDZ_6-domain) identified are known to be highly regulated during germination, maximum stem elongation, anthesis, and grain development stages. The homozygous/biallelic SNPs having allele frequency above 30% were identified for yield and crop establishment/plants m-2. These SNPs correspond to HTH myb-type and BHLH transcription factors, brassinosteroid signalling pathway, kinase activity, ATP and chitin binding activity. These resources are valuable in haplotype-based breeding and genome editing to improve yield potential on sodic-dispersive soils.

First report of pulmonary disease associated with Nicoletella semolina in a horse in New Zealand.

Case history: A 9-year-old warmblood gelding with a history of chronic intermittent tachypnoea and dyspnoea was presented for evaluation and removal of a mass on the left side of the neck. A fibrous mass adherent to the left jugular vein developed and was removed surgically 6 weeks later, at which time the owner requested an evaluation of the cause of the persistent respiratory signs first noted on primary admission. Clinical findings and treatment: Clinical findings included coarse lung sounds on thoracic auscultation, tracheal wheeze, and an abnormal trans-tracheal aspirate. These findings, in addition to the results of ultrasonographic imaging of the thorax and transtracheal cytology, were suggestive of bacterial bronchopneumonia. Initial antimicrobial therapy included I/M 22 mg/kg procaine penicillin every 12 hours and I/V 6.6 mg/kg gentamicin sulphate every 24 hours. The horse's clinical signs improved within 36 hours. It was discharged after 6 days, and at the owner's request antimicrobial therapy was changed to 25 mg/kg trimethoprim/sulphadimidine to be given orally every 12 hours for 10 days. One month later, the horse had recovered and there were no further complications reported by the owner except for an occasional cough while grazing Laboratory findings: Bacterial culture of transtracheal wash fluid resulted in the isolation of Nicoletella semolina as the sole organism, later confirmed by genotyping. Attempts to subculture the organism for antimicrobial susceptibility testing were unsuccessful. Diagnosis: Infectious bronchopneumonia associated with Nicoletella semolina Clinical relevance: Further work is required to determine whether N. semolina is acting as an opportunistic commensal of the equine respiratory tract or a primary pathogen. However, this article reports the first instance in New Zealand of an association between the presence of this organism and respiratory disease in a horse.

Catalyst-Controlled Regioselective Chlorination of Phenols and Anilines through a Lewis Basic Selenoether Catalyst.

We report a highly efficient ortho-selective electrophilic chlorination of phenols utilizing a Lewis basic selenoether catalyst. The selenoether catalyst resulted in comparable selectivities to our previously reported bis-thiourea ortho-selective catalyst, with a catalyst loading as low as 1%. The new catalytic system also allowed us to extend this chemistry to obtain excellent ortho-selectivities for unprotected anilines. The selectivities of this reaction are up to >20:1 ortho/para, while the innate selectivities for phenols and anilines are approximately 1:4 ortho/para. A series of preliminary studies revealed that the substrates require a hydrogen-bonding moiety for selectivity.

Outcomes of microdebrider-assisted versus radiofrequency-assisted inferior turbinate reduction surgery: a systematic review and meta-analysis of interventional randomised studies.

BACKGROUND: The microdebrider technique was introduced in clinical practice to provide a better outcome in nasal obstruction caused by inferior turbinate hypertrophy. We conducted this systematic review to evaluate the effectiveness of this technique, by comparison with the radiofrequency-assisted modality. METHODOLOGY: PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched to retrieve relevant randomised studies published prior to November 2019. Randomised Trials in English that studied the difference between the two techniques among adult patients were eligible for the current review. Data extraction and study inclusion were guided by PRISMA guidelines. The outcome measures were visual analogue scale (VAS, 0-10) for nasal obstruction, anterior active rhinomanometry, and acoustic rhinometry. A meta-analysis was carried out to quantify the difference between the two techni- ques, for each measured outcome. RESULTS: Seven randomised trials were included and quantitatively analysed in this meta-analysis. Our analysis revealed that the microdebrider-assisted technique demonstrated significantly better VAS (0-10) for nasal obstruction scores in early and late posto- perative follow-up. Whilst no difference was noted using the objective measurements (rhinomanometry and acoustic rhinometry) at early follow-up, microdebrider-assisted technique showed superior results in long-term follow-up, as evidenced using anterior active rhinomanometry. CONCLUSIONS: The microdebrider-assisted technique results in a better outcome, particularly in long-term follow-up, when compa- red with radiofrequency.

Improvement in lipids after switch to boosted atazanavir or darunavir in children/adolescents with perinatally acquired HIV on older protease inhibitors: results from the Pediatric HIV/AIDS Cohort Study.

OBJECTIVES: Dyslipidaemia is common in perinatally HIV-infected (PHIV) youth receiving protease inhibitors (PIs). Few studies have evaluated longitudinal lipid changes in PHIV youth after switch to newer PIs. METHODS: We compared longitudinal changes in fasting lipids [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and TC:HDL-C ratio] in PHIV youth enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) study who switched to atazanavir/ritonavir (ATV/r)- or darunavir/ritonavir (DRV/r)-based antiretroviral therapy (ART) from an older PI-based ART and those remaining on an older PI. Generalized estimating equation models were fitted to assess the association of a switch to ATV/r- or DRV/r-based ART with the rate of change in lipids, adjusted for potential confounders. RESULTS: From 2007 to 2014, 47 PHIV children/adolescents switched to ATV/r or DRV/r, while 120 remained on an older PI [primarily lopinavir/r (72%) and nelfinavir (24%)]. Baseline age ranged from 7 to 21 years. After adjustment for age, Tanner stage, race/ethnicity, and HIV RNA level, a switch to ATV/r or DRV/r was associated with a more rapid annual rate of decline in the ratio of TC:HDL-C. (ß = -0.12; P = 0.039) than remaining on an older PI. On average, TC declined by 4.57 mg/dL/year (P = 0.057) more in the switch group. A switch to ATV/r or DRV/r was not associated with the rate of HDL-C, LDL-C, or TG change. CONCLUSIONS: A switch to ATV/r or DRV/r may result in more rapid reduction in TC and the TC:HDL-C ratio in PHIV youth, potentially impacting long-term cardiovascular disease risk.

Enantioselective Functionalization of Enamides at the ß-Carbon Center with Indoles.

We report an enantioconvergent approach for the functionalization of enamides at the ß-carbon atom, which involves a chiral Brønsted acid induced tautomerization of 2-amidoallyl into 1-amidoallyl cations. These putative reactive intermediates were produced by ionization of racemic α-hydroxy enamides with a chiral Brønsted acid and captured with substituted indoles in a highly regio- and enantioselective manner.

Supramolecular Storage and Controlled Photorelease of an Oxidizing Agent using a Bambusuril Macrocycle.

The oxidizing ability of peroxodisulfate upon complexation inside the Bambusuril macrocycle cavity is inhibited. This dianionic agent can be released on demand from its stable 1:1 complex in water (log Ka =6.9 m-1 ) by addition of a more strongly bound anion, such as iodide (log Ka =7.1 m-1 ), which can also be delivered in situ upon irradiation from a 4-hydroxyphenacyl iodide derivative with spatial and temporal precision. The oxidizing properties of peroxodisulfate ions liberated from the complex recover and can take part in subsequent chemical transformations.

pH Control on the Sequential Uptake and Release of Organic Cations by Cucurbit[7]uril.

Cucurbit[7]uril (CB7) is a macrocycle with the ability to form the most stable supramolecular complexes in water ever reported for an artificial receptor. Its use for the design of advanced functional materials is, however, very limited because there is no example of a fully reversible CB7 based supramolecular complex enabling repetitious dissociation/association controlled by external stimuli. We report the synthesis of a new ferrocene amino acid that forms with CB7 a 1:1 inclusion complex that is stable in submicromolar concentration at low pH but dissociates at high pH. This reversible process was used for the sequential uptake and release of bispyridinium and antraquinone guests by CB7, which is controlled by adjusting the pH of the solution.

Laparoscopy, computerised tomography and fluorodeoxyglucose positron emission tomography in the management of gastric and gastro-oesophageal junction cancers.

BACKGROUND: The staging laparoscopy has been used in the management of gastrointestinal cancers. The aim of this study was to evaluate the role of staging laparoscopy, in comparison with computed tomography (CT) and fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in staging patients with gastro-oesophageal junction (GOJ) and gastric cancers. METHODS: The data were collected for patients between 1996 and 2013 undergoing investigation and treatment for GOJ and gastric cancers at a single institute. The pre-operative data (staging data), intraoperative details, post-operative course and follow-up were analysed for individual cases. RESULTS: Staging laparoscopy altered management plan in 64 (17 %) of 387 patients with negative staging CT and FDG-PET scan. Twenty-seven (7 %) patients with GOJ cancer (types I, II and III) were identified with pathological intraperitoneal nodes, 15 (4 %) gastric cancer with metastatic intraperitoneal deposits and liver metastases and 3 % gastric cancers with positive ascitic fluid for cancer cells. Ten (3 %) of patients were downstaged and were offered curative resection. Patients with metastatic disease were referred for palliative chemotherapy. The overall sensitivity of staging laparoscopy in diagnosing intraabdominal pathology was 86 % in comparison with CT (81 %) and FDG-PET (78 %). CONCLUSIONS: The diagnostic laparoscopy is useful for detecting and confirming nodal involvement and distant metastatic disease not evident on the staging CT scan and FDG-PET. This could potentially alter treatment and prognosis in patients with upper gastrointestinal cancer. The diagnostic laparoscopy should be performed as part of investigation and treatment planning for patients suffering from GOJ and gastric cancers. This can help to avoid surgery in patients with advanced disease.

Synthesis of Vinyl Chlorides via Triphosgene-Pyridine Activation of Ketones.

Herein, we describe a mild method to prepare aliphatic and aromatic vinyl chlorides from their corresponding ketones via triphosgene-pyridine activation in dichloromethane at reflux. The mechanism of this reaction is proposed to involve formation of a putative α-chloro pyridinium carbamate intermediate, which appeared to readily undergo E2 elimination in the presence of pyridine.

Investigation of the epithelial to mesenchymal transition markers S100A4, vimentin and Snail1 in gastroesophageal junction tumors.

Epithelial to mesenchymal transition (EMT) promotes tumor progression and invasion. As no study has focused on gastroesophageal junction (GEJ) tumors, the expression of three EMT-related proteins (S100A4, vimentin, and Snail1) was investigated with the aim of assessing their pathologic and prognostic significance. Resection specimens were obtained from 104 patients who underwent surgery for GEJ adenocarcinoma, without preoperative chemotherapy. Three tissue cores were obtained from each of the tumor body (TB), luminal surface (LS), and invasive edge (IE) to produce tissue microarrays, and immunohistochemical staining was performed. The microarrays were scored independently by two observers. The demographic and histopathologic details of the patients were collected. Overall positive expression was observed in 88 (S100A4, 85%), 16 (vimentin, 14%), and 92 (Snail1, 89%) tumors. Staining for S100 A4 was positive in 79 (76%) of TB, 69 (66%) of IE, and 69 (66%) of LS specimens. Staining for vimentin was positive in 7 (6%) of TB, 11 (11%) of IE, and 5 (5%) of LS specimens. Staining for Snail1 was positive in 83 (80%) of TB, 51 (49%) of IE, and 78 (75%) of LS specimens. Positive staining of TB for S100A4 (P = 0.04) and Snail1 at IE (P = 0.01) was associated with involvement of circumferential resection margins. Positive staining for S100A4 in the TB (P = 0.02) and LS (P = 0.01) was associated with poor 5-year overall survival. Vimentin had no statistically significant relationships with pathologic factors or outcome. The acquisition of mesenchymal protein S100A4 is associated with a poor prognosis in patients with GEJ tumors who undergo potentially curative surgery, and LS samples can be used to obtain prognostic information. Increased EMT-related protein expression (S100A4, Snail1) is associated with the involvement of circumferential resection margin.

Social Disadvantage and Multimorbidity Including Oral Conditions in the United States.

Existing studies on multimorbidity have largely excluded oral diseases in multimorbidity prevalence estimates. The reason behind this is somewhat unclear, as chronic oral conditions are highly prevalent, affecting over half the global population. To address this gap, we examined the relationship between social disadvantage and multimorbidity, stratifying by the inclusion and exclusion of oral conditions. For participants aged 30 y and over (n = 3,693), cross-sectional analysis was carried out using the US National Health and Nutrition Survey (2013-2014). Multimorbidity was defined as having 2 or more chronic conditions. Five medical conditions were examined: diabetes, asthma, arthritis, cardiovascular disease, and depression, as well as 4 oral health conditions: caries, periodontal disease, number of teeth, and edentulousness. Education and income poverty ratio were selected as measures of social disadvantage. Multimorbidity prevalence estimates according to social disadvantage were analyzed on an absolute and relative scale using inverse probability treatment weighting (IPTW), adjusting for age, sex, and ethnicity. The inclusion of oral health conditions in the assessment of multimorbidity increased the overall prevalence of multimorbidity from 20.8% to 53.4%. Findings from IPTW analysis demonstrated clear social gradients for multimorbidity estimates stratified by the exclusion of oral conditions. Upon inclusion of oral conditions, the prevalence of multimorbidity was higher across all social groups for both education and income. Stratifying by the inclusion of oral conditions, the mean probability of multimorbidity was 27% (95% confidence interval [CI], 23%-30%) higher in the low-education group compared to the high-education group. Similarly, the mean probability of multimorbidity was 44% (95% CI, 40%-48%) higher in the low-income group. On a relative scale, low education was associated with a 1.52 times (95% CI, 1.44-1.61) higher prevalence of multimorbidity compared to high education. Low income was associated with a 2.18 (95% CI, 1.99-2.39) higher prevalence of multimorbidity. This novel study strongly supports the impact of chronic oral conditions on multimorbidity prevalence estimates.

High-fidelity, low-cost synthetic training model for fetoscopic spina bifida repair.

BACKGROUND: Fetoscopic spina bifida repair is increasingly being practiced, but limited skill acquisition poses a barrier to widespread adoption. Extensive training in relevant models, including both ex vivo and in vivo models may help. To address this, a synthetic training model that is affordable, realistic, and that allows skill analysis would be useful. OBJECTIVE: This study aimed to create a high-fidelity model for training in the essential neurosurgical steps of fetoscopic spina bifida repair using synthetic materials. In addition, we aimed to obtain a cheap and easily reproducible model. STUDY DESIGN: We developed a 3-layered, silicon-based model that resemble the anatomic layers of a typical myelomeningocele lesion. It allows for filling of the cyst with fluid and conducting a water tightness test after repair. A compliant silicon ball mimics the uterine cavity and is fixed to a solid 3-dimensional printed base. The fetal back with the lesion (single-use) is placed inside the uterine ball, which is reusable and repairable to allow for practicing port insertion and fixation multiple times. Following cannula insertion, the uterus is insufflated and a clinical fetoscopic or robotic or prototype instruments can be used. Three skilled endoscopic surgeons each did 6 simulated fetoscopic repairs using the surgical steps of an open repair. The primary outcome was surgical success, which was determined by water tightness of the repair, operation time <180 minutes and an Objective Structured Assessment of Technical Skills score of ≥18 of 25. Skill retention was measured using a competence cumulative sum analysis of a composite binary outcome of surgical success. Secondary outcomes were cost and fabrication time of the model. RESULTS: We made a model that can be used to simulate the neurosurgical steps of spina bifida repair, including anatomic details, port insertion, placode release and descent, undermining of skin and muscular layer, and endoscopic suturing. The model was made using reusable 3-dimensional printed molds and easily accessible materials. The 1-time startup cost was €211, and each single-use, simulated myelomeningocele lesion cost €9.5 in materials and 50 minutes of working time. Two skilled endoscopic surgeons performed 6 simulated, 3-port fetoscopic repairs, whereas a third used a Da Vinci surgical robot. Operation times decreased by more than 30% from the first to the last trial. Six experiments per surgeon did not show an obvious Objective Structured Assessment of Technical Skills score improvement. Competence cumulative sum analysis confirmed competency for each surgeon. CONCLUSION: This high-fidelity, low-cost spina bifida model allows simulated dissection and closure of a myelomeningocele lesion. VIDEO ABSTRACT.

Manufacturing and preclinical toxicity of GLP grade gene deleted attenuated Leishmania donovani parasite vaccine.

Centrin1 gene deleted Leishmania donovani parasite (LdCen1-/-) was developed and extensively tested experimentally as an intracellular stage-specific attenuated and immunoprotective live parasite vaccine candidate ex vivo using human PBMCs and in vivo in animals. Here we report manufacturing and pre-clinical evaluation of current Good-Laboratory Practice (cGLP) grade LdCen1-/- parasites, as a prerequisite before proceeding with clinical trials. We screened three batches of LdCen1-/- parasites manufactured in bioreactors under cGLP conditions, for their consistency in genetic stability, attenuation, and safety. One such batch was preclinically tested using human PBMCs and animals (hamsters and dogs) for its safety and protective immunogenicity. The immunogenicity of the CGLP grade LdCen1-/- parasites was similar to one grown under laboratory conditions. The cGLP grade LdCen1-/- parasites were found to be safe and non-toxic in hamsters and dogs even at 3 times the anticipated vaccine dose. When PBMCs from healed visceral leishmaniasis (VL) cases were infected with cGLP LdCen1-/-, there was a significant increase in the stimulation of cytokines that contribute to protective responses against VL. This effect, measured by multiplex ELISA, was greater than that observed in PBMCs from healthy individuals. These results suggest that cGLP grade LdCen1-/- manufactured under cGMP complaint conditions can be suitable for future clinical trials.

Comparison of the prognostic value of the 6th and 7th editions of the Union for International Cancer Control TNM staging system in patients with lower esophageal cancer undergoing neoadjuvant chemotherapy followed by surgery.

Carcinoma of the esophagus is classified according to the Union for International Cancer Control (UICC) TNM staging system. The 7th edition of the UICC TNM staging system was published in 2009. This is the first study to compare the prognostic value of the TNM 6th and 7th editions in patients with esophageal carcinoma treated with chemotherapy followed by surgery. Two hundred forty-three patients with esophageal carcinoma were retrospectively selected from two referral centers. All patients received chemotherapy before surgery. Histopathologic data from the resection specimens were retrieved and restaged according to the TNM 7th edition. Disease-specific survival curves were plotted for depth of tumor invasion (ypT), lymph node status (ypN), and ypTNM stage and then compared. Median follow-up after surgery was 2.5 years (range 0.2-9 years). Survival analysis using the log-rank method revealed that there was a significant difference in survival between ypT4 disease and ypT3 disease (P= 0.003), but no difference between ypT0, ypT1, ypT2, and ypT3 categories irrespective of TNM edition used. Survival probability was significantly different between ypN0 and ypN1 (P= 0.001 for TNM 6th and 7th edition), as well as ypN2 and ypN3 (TNM 7th edition, P= 0.004), but not between ypN1 and ypN2 (TNM 7th edition, P= 0.89). Neither the TNM 6th nor 7th edition T staging provides accurate survival probability stratification. However, the advantage of the 7th edition is the introduction of a third tier in survival stratification for patients with nodal involvement.

Estimating the prevalence of pediatric hematological malignancies in Al-Madinah Al-Munawwarah, Saudi Arabia.

OBJECTIVES: To provide an updated estimate to the prevalence of pediatric hematological malignancies (HMs) in the Al-Madinah Al-Munawwara, Saudi Arabia. METHODS: This is a retrospective study that was carried out between 2016 and 2022. The study population was comprised of 171 children under 16 who had been diagnosed with HMs. The data was compiled from King Salman Medical City's Maternity and Children's Hospital, Al-Madinah Al-Munawwarah, Saudi Arabia. RESULTS: Among the 171 HM patients (64% males and 36% females), 13 subtypes were identified, with B-cell acute lymphoblastic leukemia having the highest incidence (70.3%). Acute myelomonocytic leukemia (8.7%), T-cell acute lymphoblastic leukemia (4.7%), and acute promyelocytic leukemia (3.5%) were the next most common types of HMs. Other rare cases were also found. CONCLUSION: Prevalence rate can be utilized to monitor the progression of disease incidence. Here, HMs demonstrated a pattern of increasing incidence in males over a 7-year period, with a higher rate in early childhood. There were 13 types of HMs diagnosed, with B-acute lymphocytic leukemia having the highest incidence. Although juvenile cancer is rare, it is nonetheless a significant cause of mortality in children. A successful prognosis requires prompt and accurate diagnosis and treatment.

Toxoplasma gondii, HBV, and HCV co-infection and their correlation with CD4 cells among Iranian HIV-positive patients.

INTRODUCTION: Human immunodeficiency virus (HIV/AIDS) infected patients have a higher risk of opportunistic infections (OIs) depending on their immunological status, especially CD4 + cell count. Toxoplasma gondii, hepatitis C virus (HCV), and hepatitis B virus (HBV) are important OIs among Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) patients. However, little is known about co-infection of these pathogens among HIV-infected individuals and their correlation with the patient's CD4 + cell count. Hence, this study aimed to investigate the serological and molecular status of T. gondii infection among HIV-infected individuals who had co-infection with HBV and HCV infections. METHODS: A total of 100 HIV/AIDS patients in two cities in the southwest of Iran was tested for T. gondii Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies as well as DNA detection by polymerase chain reaction (PCR) targeting the RE gene. HBV and HCV were detected by hepatitis B surface antigen (HBsAg) test, hepatitis C antibody (HCV Ab) test, and Real-Time PCR. The number of CD4 + cell counts was determined by Flow cytometry. RESULTS: Anti-T. gondii IgG was positive in 22% of the patients, but anti-T. gondii IgM and PCR were negative in all samples. HBV and HCV were positive in 8% and 33% of the patients, respectively. Co-infections were as followed: HIV + HCV (16%), HIV + HCV + T. gondii (11%), HIV + T. gondii (5%), HIV + HBV (1%), HIV + HBV + T. gondii (1%), HIV + HBV + HCV (1%), and HIV + HBV + HCV + T. gondii (5%). A significant decline in CD4 + cell counts was found in such co-infection groups (HIV + T. gondii, HIV + HCV + T. gondii, and HIV + HBV + HCV + T. gondii) compared with the HIV mono-infection group. CONCLUSIONS: Our study showed that co-infections of T. gondii, HCV, and HBV were common among HIV-infected patients and co-infections had a negative correlation with CD4 + cell counts of the patients.