LEOPOLDOVI HVATOVI: KOLIKO SU ČESTI U NAŠOJ SVAKODNEVNOJ PRAKSI

Objective. To determine how frequent obstetricians use Leopold’s maneuvers in their practice. Subjects and Methods. A questionnaire with numerical scale was distributed among practicing obstetricians. They examined how ­frequent the symphyseal fundal height (SFH) measurement, Leopold’s maneuvers and ultrasound examination for fetal orientation were performed. Results. A total of 165 obstetricians completed the questionnaire. Only 56 (33.9%) respondents indicated that they use SFH. The first and third Leopold’s maneuver were the most frequent abdominal grips ­performed. Only 36 (21.8%) respondents regularly perform all four maneuvers. Seventy seven (46.7%) respondents use ultrasound to determine fetal orientation. The use of ultrasound was significantly higher (p=0.02) in those practicing for less than 10 years (62.6%) compared to those practicing for 10 years or more (43.3%). Conclusion. Leopold’s maneuvers are still common in daily obstetrics practice. Abdominal palpation remains a common method to estimate the uterine size. The first and third Leopold’s maneuver were the most frequent abdominal grips performed. Ultrasound examination is commonly used to determine fetal orientation.Cilj rada je ustanoviti koliko često opstetričari u svojoj praksi rabe Leopold-Pavlikove hvatove. Materijal i metode. Upitnik s brojčanim podatcima je podijeljen opstetričarima iz prakse. Oni su pokazali koliko često izvode ­mjerenje udaljenosti fundus simfiza, Leoplodove hvatove i pregled ultrazvukom za prosudbu fetalnog položaja i stava. Rezultati. Ukupno je 165 opstetričara ispunilo upitnik. Samo 56 (33,9%) njih mjere udaljenost fundus simfiza. Prvi i treći Leopoldov hvat su najčešće rabljeni hvatovi. Samo 36 (21,8%) ispitanika redovito izvode sva četiri hvata. Sedamdeset ­sedam (47,7%) rabe ultrazvučni pregled da odrede položaj i stav djeteta. Uporaba ultrazvuka je bila signifikantno češća (p=0,02) u onih koji rade manje od 10 godina (62,6%) od onih koji rade dulje od 10 godina (43,3%). Zaključak. Leopoldovi hvatovi su još uvijek uobičajeni u svakodnevnoj opstetričnoj praksi. Palpacija trbuha trudnice je uobičajena metoda za prosudbu veličine maternice. Prvi i treći Leopoldov hvat su najčešće rabljeni hvatovi. Pregled ultrazvukom se obično rabi za prosudbu položaja i stava fetusa

Oral Human Papillomavirus Prevalence and Genotyping Among a Healthy Adult Population in the US

IMPORTANCE In the US, oropharyngeal cancer, predominantly caused by high-risk (HR) human papillomavirus (HPV) infection, is the most frequent HPV-associated cancer, surpassing cervical cancer. However, little is known about oral HPV prevalence and genotype distribution in the general population. OBJECTIVE To assess oral HPV prevalence and factors associated with HR and low-risk infection in a general US population. DESIGN, SETTING, AND PARTICIPANTS PROGRESS (Prevalence of Oral HPV Infection, a Global Assessment) was a cross-sectional observational study conducted between November 2021 and March 2022 in 43 dental offices in the US (24 urban, 13 urban cluster, and 6 rural sites), spanning 21 states. Eligible participants were aged 18 to 60 years, visiting dental clinics for routine dental examination. Dental clinics used targeted sampling to recruit equal distributions of men and women and across age groups. EXPOSURE Participants provided an oral gargle specimen for HPV DNA and genotyping and completed behavioral questionnaires, and dentists reported oral health status. Detection of HPV DNA and genotyping was performed using the SPF10/DEIA/LiPA25 system at a central laboratory. MAIN OUTCOME Oral HPV prevalence. RESULTS Of the 3196 participants enrolled, mean (SD) age was 39.6 (12.1) years, and 55.5% were women. Oral HPV prevalence was 6.6%(95% CI, 5.7%-7.4%) for any HPV genotype, and 2.0% (95% CI, 1.5%-2.5%), 0.7%(95% CI, 0.4%-1.0%), and 1.5%(95% CI, 1.1%-1.9%) for HR, HPV-16, and 9-valent-HPV vaccine types, respectively. Among HPV-positive participants, HPV-16 was the most prevalent genotype (12.4% among men and 8.6% among women). Prevalence of HPV was higher in men than women and highest among men aged 51 to 60 years (16.8%, 6.8%, and 2.1% for any HPV, HR HPV, and HPV-16, respectively). Factors associated with HR oral infection included being male (adjusted odds ratio [AOR], 3.1; 95% CI, 1.2-8.5), being aged 51 to 60 years (AOR, 3.3; 95% CI, 1.5-7.3), having 26 or more lifetime male sex partners (AOR, 6.5; 95% CI, 2.3-18.7), and having 6 to 25 lifetime female oral sex partners (AOR, 3.4; 95% CI, 1.3-8.7). CONCLUSIONS AND RELEVANCE In this cross-sectional study, oral HPV burden was highest among older men who may be at higher risk of developing oropharyngeal cancer. In addition to male sex and older age, HR oral HPV infection was also associated with sexual behaviors, including increasing number of male sex partners and female oral sex partners

Analysis of the Origin of Emiratis as Inferred from a Family Study Based on HLA-A, -C, -B, -DRB1, and -DQB1 Genes

In this study, we investigated HLA class I and class II allele and haplotype frequencies in Emiratis and compared them to those of Asian, Mediterranean, and Sub-Saharan African populations. Methods: Two-hundred unrelated Emirati parents of patients selected for bone marrow transplantation were genotyped for HLA class I (A, B, C) and class II (DRB1, DQB1) genes using reverse sequence specific oligonucleotide bead-based multiplexing. HLA haplotypes were assigned with certainty by segregation (pedigree) analysis, and haplotype frequencies were obtained by direct counting. HLA class I and class II frequencies in Emiratis were compared to data from other populations using standard genetic distances (SGD), Neighbor-Joining (NJ) phylogenetic dendrograms, and correspondence analysis. Results: The studied HLA loci were in Hardy-Weinberg Equilibrium. We identified 17 HLA-A, 28 HLA-B, 14 HLA-C, 13 HLA-DRB1, and 5 HLA-DQB1 alleles, of which HLA-A*02 (22.2%), -B*51 (19.5%), -C*07 (20.0%), -DRB1*03 (22.2%), and -DQB1*02 (32.8%) were the most frequent allele lineages. DRB1*03~DQB1*02 (21.2%), DRB1*16~DQB1*05 (17.3%), B*35~C*04 (11.7%), B*08~DRB1*03 (9.7%), A*02~B*51 (7.5%), and A*26~C*07~B*08~DRB1*03~DQB1*02 (4.2%) were the most frequent two- and five-locus HLA haplotypes. Correspondence analysis and dendrograms showed that Emiratis were clustered with the Arabian Peninsula populations (Saudis, Omanis and Kuwaitis), West Mediterranean populations (North Africans, Iberians) and Pakistanis, but were distant from East Mediterranean (Turks, Albanians, Greek), Levantine (Syrians, Palestinians, Lebanese), Iranian, Iraqi Kurdish, and Sub-Saharan populations. Conclusions: Emiratis were closely related to Arabian Peninsula populations, West Mediterranean populations and Pakistanis. However, the contribution of East Mediterranean, Levantine Arab, Iranian, and Sub-Saharan populations to the Emiratis' gene pool appears to be minor.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors in the UAE. This work was supported by the National Institutes of Health (NIH) and National Institute of Allergy and Infectious Disease (NIAID), grant R01AI128775 (SJM). The content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIAID, NIH, and United States government.Scopu

Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis

Background p16(INK4a) (p16) immunohistochemistry is the most widely used biomarker assay for inferring HPV causation in oropharyngeal cancer in clinical and trial settings. However, discordance exists between p16 and HPV DNA or RNA status in some patients with oropharyngeal cancer. We aimed to clearly quantify the extent of discordance, and its prognostic implications. Methods In this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer; data on p16 immunohistochemistry and on HPV testing; information on age, sex, tobacco, and alcohol use; staging by TNM 7th edition; information on treatments received; and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors. Findings Our search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74middot7%) of 7654 patients were male and 1940 (25middot3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10middot9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions (r=-0middot744, p=0middot0035). The proportion of patients with p16+/HPV- oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29middot7% vs 9middot0%, p<0middot0001). 5-year overall survival was 81middot1% (95% CI 79middot5-82middot7) for p16+/HPV+, 40middot4% (38middot6-42middot4) for p16-/HPV-, 53middot2% (46middot6-60middot8) for p16-/HPV+, and 54middot7% (49middot2-60middot9) for p16+/HPV-. 5-year disease-free survival was 84middot3% (95% CI 82middot9-85middot7) for p16+/HPV+, 60middot8% (58middot8-62middot9) for p16-/HPV-; 71middot1% (64middot7-78middot2) for p16-/HPV+, and 67middot9% (62middot5-73middot7) for p16+/HPV-. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort. Interpretation Patients with discordant oropharyngeal cancer (p16-/HPV+ or p16+/HPV-) had a significantly worse prognosis than patients with p16+/HPV+ oropharyngeal cancer, and a significantly better prognosis than patients with p16-/HPV- oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd

Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis

Background: p16INK4a (p16) immunohistochemistry is the most widely used biomarker assay for inferring HPV causation in oropharyngeal cancer in clinical and trial settings. However, discordance exists between p16 and HPV DNA or RNA status in some patients with oropharyngeal cancer. We aimed to clearly quantify the extent of discordance, and its prognostic implications. Methods: In this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer; data on p16 immunohistochemistry and on HPV testing; information on age, sex, tobacco, and alcohol use; staging by TNM 7th edition; information on treatments received; and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors. Findings: Our search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74·7%) of 7654 patients were male and 1940 (25·3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10·9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions (r=–0·744, p=0·0035). The proportion of patients with p16+/HPV– oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29·7% vs 9·0%, p<0·0001). 5-year overall survival was 81·1% (95% CI 79·5–82·7) for p16+/HPV+, 40·4% (38·6–42·4) for p16–/HPV–, 53·2% (46·6–60·8) for p16–/HPV+, and 54·7% (49·2–60·9) for p16+/HPV–. 5-year disease-free survival was 84·3% (95% CI 82·9–85·7) for p16+/HPV+, 60·8% (58·8–62·9) for p16–/HPV–; 71·1% (64·7–78·2) for p16–/HPV+, and 67·9% (62·5–73·7) for p16+/HPV–. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort. Interpretation: Patients with discordant oropharyngeal cancer (p16–/HPV+ or p16+/HPV–) had a significantly worse prognosis than patients with p16+/HPV+ oropharyngeal cancer, and a significantly better prognosis than patients with p16–/HPV– oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions

THE THEORY OF GHARAR (RISK AND UNCERTAINTY) IN ISLAMIC LAW A Major Cause of Disputes in Construction Contracts

There is widespread interest in the applications of Islamic law in construction contracts. This is due to the ongoing construction boom in many countries in the Middle East whose civil codes are based on Islamic law. This paper addresses the applications of an important theory in the Islamic law of transactions to construction contracts. This theory of gharar – normally translated as risk and uncertainty- has wide ranging applications in the field of construction law. The paper defines gharar and summarises its basic principles. It then goes on to introduce the essentials of a valid contract in Islamic law. These essentials are then related to the contract documents normally used in construction contracts. Based on this, five specific practical applications of the theory of gharar in construction contracts are elaborated, and illustrated with some case studies. The paper concludes that risks and uncertainties are inherent in construction contracts, due to the special nature and complexity of these contracts. These risks and uncertainties tend to lead to conflict and disputes. The theory of gharar places a limit on the level of risk and uncertainty that is acceptable in contracts of exchange. Exceeding this limit leads to invalidity of the contract. The theory of gharar, therefore, has a major role to play in the prevention and resolution of construction disputes. It is of vital importance that those involved in the drafting and execution of construction contracts- be they construction lawyers or engineers- understand this theory and its applications. Keywords: Construction law, Islamic law, construction contracts, dispute prevention, dispute resolution, risk management

Transplacental transfer of 2-naphthol in human placenta

Objective: To determine the transfer of 2-naphthol (2-NPH) in fullterm human placental tissues. Methods: Six placentas were studied. The ex-vivo dual closed-loop human placental cotyledon perfusion model was used. 2-NPH was added to the perfusate in the maternal compartment. Samples were obtained from the maternal and fetal up to 360 min measuring. Results: The mean fetal weight was 2880 ± 304.2 g. Mean perfused cotyledon weight was 26.3 (±5.5) g. All unperfused placental tissue samples contained NPH with a mean level of 7.98 (±1.73) μg\g compared to a mean of 15.58 (±4.53) μg\g after 360 min perfusion. A rapid drop in maternal 2-NPH concentration was observed; from 5.54 μg\g in the first 15 min and 13.8 μg\g in 360 min. The fetal side increased from 0.65 μg\g in the initial 15 min to 1.5 μg\g in 360 min. The transfer rate of NPH was much lower than that of antipyrine. Conclusion: 2-NPH has the ability to rapidly across the placenta from the maternal to the fetal compartment within 15 min. The placenta seems to play a role in limiting the passage of 2-NPH in the fetal compartment

Caesarean scar pregnancy: time to explore indications of the caesarean sections?

A retrospective study was conducted in women with history of a caesarean scar pregnancy (CSP) to explore the possible causative mechanisms. Over a period of 40 months, a total of 16,926 deliveries and 3554 caesarean sections (CS) occurred in our hospital. Nine cases of CSP were identified at an incidence of 1:1880 births and 0.25% of all CS. Analysis of the indications of the previous CS revealed that 88.8% of women with known indication had undergone CS without labour. Out of them, 75% underwent CS at preterm gestation and 25% had term elective procedure for breech presentation. Of the patients, 77.7% had multiple CS. Conservation of the uterus was possible in 77.7% of patients utilising non-radical forms of treatment. As most of the women underwent CS with a non-contractile uterus without labour, we believe that the risk of CSP may be related to the indications of the previous CS as the number of CS alone could not explain the occurrence of CSP. It is time to explore this area so that screening strategies can be developed to detect CSP at the earliest possible gestation and to prevent life-threatening complications such as uterine rupture and severe hemorrhage.Impact statement What is already known on this subject? A caesarean scar pregnancy (CSP) is a life-threatening condition that can result in uterine rupture and in severe haemorrhage. Although the diagnostic criteria for the CSP have been established, the risk factors that favour the condition are not well understood. We know that the incomplete healing of the lower uterine segment (LUS) from poor vascularisation can create a microscopic dehiscent tract through which the blastocyst enters the myometrium. Some have postulated that the healing processes following the elective procedures, such as for breech deliveries performed in a non-developed LUS, might facilitate this process. What do the results of this study add? In this study, analysis of the indications of the previous CS revealed that majority of women with a known indication had undergone CS without labour, either at preterm gestation or term elective procedure for breech presentation. We have postulated the possible causative mechanisms in relation to the physiology of LUS development. To the best of our knowledge, this is the first study that has looked specifically at the relationship between the indications of previous CS and CSP. What are the implications of these findings for clinical practice and/or further research? Further studies exploring the indications of the previous CS are recommended so that early first-trimester screening strategies can be generated towards this subgroup of patients to detect CSP at the earliest possible gestation