The risk of shoulder dystocia related permanent fetal injury in relation to birth weight

OBJECTIVE: To examine birth weight related risks of fetal injury in connection with shoulder dystocia. STUDY DESIGN: The investigation was based on a retrospective analysis of 316 fetal neurological injuries associated with deliveries complicated by arrest of the shoulders that occurred across the United States. RESULTS: The study revealed that the distribution of birthweights for the high risk shoulder dystocia population differs from the standard birthweight distribution. The relative difference per birthweight interval is used to adjust an assumed 1:1000 baseline risk of injury due to shoulder dystocia following vaginal deliveries. These adjusted risks show a need to consider new thresholds for elective cesarean delivery. CONCLUSIONS: Current North American and British guidelines, that set 5000 g as minimum estimated fetal weight limit for elective cesarean section in non-diabetic and 4500 g for diabetic gravidas, may expose some macrosomic fetuses to a high risk of permanent neurological damage. The authors present the opinion that the mother, having been informed of the risks of vaginal versus abdominal delivery, should be allowed to play an active role in the critical management decisions.     

Shoulder dystocia related fetal neurological injuries: the predisposing roles of forceps and ventouse extractions

On the basis of 333 documented cases of permanent perinatal neurological damage, associated with arrest of the shoulders at birth, the authors conducted a retrospective study in order to evaluate the predisposing role, if any, of the utilization of extraction instruments. The investigation revealed that 35% of all injuries occurred in neonates delivered by forceps, ventouse or sequential ventouse–forceps procedures. This frequency was several-fold higher than the prevailing instrument use in the practices of American obstetricians during the same years. A high rate of forceps and ventouse extractions was demonstrable in all birth weight categories. Average weight and moderately large for gestational age fetuses underwent instrumental extractions more often than grossly macrosomic ones. This circumstance indicates that forceps and ventouse are independent risk factors, unrelated to fetal size. Their use entailed central nervous system injuries significantly more often than did spontaneous deliveries. The findings suggest that extraction procedures may be as important as macrosomia among the factors that lead to neurological damage in the child in connection with shoulder dystocia. Because they augment the intrinsic dangers of excessive fetal size exponentially, the authors consider their use in case of ≥4,000 g estimated fetal weight inadvisable. Sequential forceps–ventouse utilization further doubles the risks and is, therefore, to be avoided in all circumstances.     

Three-dimensional ultrasound imaging of the levator hiatus in late pregnancy and associations with delivery outcomes

OBJECTIVE: To determine the correlations between dimensions of the levator hiatus in late pregnant nulliparous women, mode of delivery and length of second stage. METHODS: This was a prospective observational pilot study of 61 nulliparous women seen and examined between 36 and 40 weeks of pregnancy. A translabial ultrasound examination was undertaken, and three-dimensional volumes comprising the levator hiatus were recorded at rest, during a pelvic floor muscle contraction and on Valsalva. The volumes were analysed in a blinded fashion using proprietary software to determine linear dimensions and hiatal area. Information regarding delivery outcomes and course of labour was obtained from the obstetric database. Statistical analysis was undertaken for correlations between hiatal dimensions and labour outcomes. RESULTS: No consistent correlations were found between levator dimensions and delivery mode. However, an inverse correlation was demonstrated between the area of the hiatus, particularly on pelvic floor contraction, and length of total second stage. CONCLUSIONS: Levator hiatal dimensions are associated with the length of the second stage of labour. Although the numbers were small, our findings suggest that the effect of pelvic floor structures on progress in labour is worth further study.     

Impact of clinic interventions on the rate of influenza vaccination in pregnant women

OBJECTIVE: To assess the impact of interventions in a prenatal clinic on the influenza vaccination rate in pregnant women. STUDY DESIGN: This retrospective study of women receiving care in a university prenatal clinic examined the impact of several interventions to increase immunization rates implemented over 2 years. Influenza vaccination rates were assessed before and after the interventions, which included provider and staff education, stocking of the vaccine in the clinic and implementation of standing orders. RESULTS: Influenza vaccination rates in pregnant women increased from <1% to 37%. Standing orders were the most important intervention for increasing immunization rates. Patients who received care in the certified nurse midwife clinic were more likely to be vaccinated, while those who received care in a high-risk obstetric clinic were less likely. CONCLUSION: Interventions to improve influenza vaccination rates among pregnant women, particularly standing orders, are effective. These interventions should be implemented nationally in all prenatal care clinics.     

Relación entre los valores de hemoglobina materna en el primer trimestre del embarazo y recién nacidos pequeños para la edad gestacional

Objective

To evaluate maternal hemoglobin (Hb) levels in the first trimester of pregnancy in patients with a history of small-for-gestational-age (SGA) infants and to compare these levels with those in a control group with appropriate-for-gestational-age (AGA) infants in order to determine the influence of Hb levels on intrauterine fetal growth.

Material and methods

From January 1999 to July 2001, 2973 live newborns were studied, of which 85 were SGA. Of these, only 52 met the inclusion criteria. First-trimester maternal Hb levels were compared between the mothers of the 52 SGA infants and 104 controls with AGE infants. A casecontrol study was performed with a ratio of 1:2. AGE was defined according to Argentinian intrauterine growth curves.

Results

The prevalence of SGA was 2.86% (95% CI: 0.27%-5.45%). Hb levels were compared between the two groups. The percentage of Hb values lower than 13 mg was higher in cases than in controls (67.3% vs 58.7%, respectively) but this difference was not statistically significant (p = 0,29; 95% CI: 0.68%-3.10%). Maternal age and prematurity did not appear to influence intrauterine fetal growth.

Conclusion

In our population, maternal Hb levels did not significantly affect intrauterine fetal growth.     

Accidental ingestion of sodium molybdate at the workplace followed by short-term biomonitoring

Introduction:Most of the molybdenum (Mo) is used in metallurgical applications, the tetrathiomolybdate form is an experimental chelating agent for Wilson’s disease. Human data of acute Mo exposure are lacking and, no report of no-observed-adverse-effect level (NOAEL) has been described until now.Case study:We report a case of acute occupational exposure to molybdenum, with the related plasma and urine molybdenum concentrations, caused by an accidental ingestion of a sip of an anti-corrosion liquid for metal containing sodium molybdate. Our purpose was to evaluate potential systemic toxicity of molybdenum and to evaluate the dose-response/dose-effect relationship. We estimated the amount of ingested molybdenum to make a mg/kg relationship and performed repeated urine and plasma molybdenum determinations. The patient was hospitalized for three days to monitor possible development of acute symptoms/biochemical alterations.Discussion:We estimated the amount of the sip around 50 ml, with an estimation of a total of 5 gr of sodium molybdate that, for the patient bodyweight of 80 kg, would mean 62,5 mg/kg of ingested Mo. Blood and urine samples collected 2 hours after ingestion showed 50 mcg/L (reference range: 0.43 – 1.8 mcg/L) and 630 mcg/L (refence range: up to 116 mcg/L) of Mo respectively, confirming acute exposure. The patients remained asymptomatic confirming that an estimated oral dose of Mo of 62.5 mg/kg was not associated with adverse effects.Conclusions:Our value, being extrapolated by a single case, will require further confirmations from other studies to allow a full evaluation of a NOAEL. Nevertheless, it does not preclude its use in evaluating the probable absence of adverse effect in the context of acute Mo exposure.     

Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HR_log2?=?1.06, 95% CI 0.99–1.14) or in men (HR_log2?=?0.97, 95% CI 0.90–1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HR_log2?=?0.91, 95% CI 0.85–0.97) and positively associated with rectal cancer in women (HR_log2?=?1.10, 95% CI 1.02–1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.     

Mechanism of voltage sensing in Ca2+- and voltage-activated K+ (BK) channels

In neurosecretion, allosteric communication between voltage sensors and Ca²⁺ binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. Significantly, the energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). Molecular dynamics simulations and proton transport experiments in the hyperpolarization-activated R210H mutant suggest that the electric field drops off within a narrow septum whose boundaries are defined by the gating charges. Unlike Kv channels, the charge movement in BK appears to be limited to a small displacement of the guanidinium moieties of R210 and R213, without significant movement of the S4.

Excitable tissues accomplish their signaling functions thanks in part to the interplay of several voltage-sensitive ion channels (1–6). Hence, to understand these processes, it is crucial to establish how voltage-sensitive ion channels sense changes in the electric field across the membrane, an issue that has been a matter of extensive study and intense debate for decades. The most widely accepted mechanism proposes the existence of voltage-sensor domains (VSDs), modules that undergo two or more discrete conformational states in response to changes in the membrane voltage. The simplest model considers two states: active (A), which promotes pore opening, and resting (R), which promotes channel closing. To accomplish its function, VSDs contain voltage-sensitive particles, which move in response to changes in the electric field. This movement triggers the interconversion between the two discrete conformational states. These voltage-sensing particles are typically the guanidine groups of arginine residues within the S4 transmembrane segment, which undergo a combination of rotational, translational, and tilting movement in response to changes in membrane voltage (7–14).The large-conductance Ca²⁺- and voltage-activated K⁺ (BK) channels have a wide distribution in mammalian tissues (15–18), where they participate in a diversity of physiological processes. Their malfunction is often related to diverse pathological conditions (19, 20). BK channel open probability is independently regulated by membrane depolarization and intracellular Ca²⁺ concentration (21, 22), each stimulus being detected by specialized modules. Like other voltage-sensitive K⁺ (Kv) channels, BK is an homotetramer in which each of its α subunits consists of a pore domain (PD; S5-S6 transmembrane segments), a voltage-sensing domain (VSD; S1–S4 transmembrane segments) containing a positively charged S4, and a cytosolic C-terminal regulatory domain, which contains the Ca²⁺-binding sites (23, 24). Also, like some members of other K⁺ channel families (25, 26), the VSD and PD of BK are non–domain swapped (23, 24). BK channels display some distinctive structural and functional features: Despite sharing the selectivity filter sequence with Kv channels, BK unitary conductance and selectivity are exquisitely high (27–30). The BK α subunit has an additional transmembrane segment S0 [therefore, its N terminus faces the extracellular medium (31)], and the voltage sensitivity in BK channels is significantly lower than that of Kv channels, presumably because of their lower number of gating charges (32).Although thoroughly studied, research into BK VSD and its voltage dependence has faced several technical obstacles. The relatively small gating charge per channel (32) and the large conductance of the BK pore makes isolating of the gating currents from the ionic currents a tough experimental challenge. In addition, because mutations of VSD residues can produce very large shifts in both the gating charge-voltage (Q(V)) and the conductance-voltage G(V)) relationships (33), it is necessary to use extreme voltages to accurately measure the voltage dependence of some mutants. Consequently, the identification of BK gating charges has been addressed by using indirect approaches (33, 34). The combination of electrophysiology measurements and kinetic modeling suggests a decentralized VSD in the BK channel, where four charged residues (D153 and R167 in S2, D186 in S3, and R213 in S4) act as voltage sensor particles (33). A recent report of the atomistic cryo-electron microscopy (cryo-EM) structures of the human BK channel and its homolog in Aplysia californica (AcSlo) revealed minor structural differences between the VSD in both the Ca²⁺-bound (open pore) and the Ca²⁺-unbound (closed pore) conformations (23, 24, 35). This result can be explained if the conformational changes of the BK VSD upon activation are small compared to those that occur during the activation of other channels, such as HCN channels (12–14).In this study, we identified voltage-sensing particles in the BK channel by using a direct functional approach, involving gating of current measurements and analysis of the Q(V) curves spanning 800 mV in the voltage axis. Systematic neutralization of the individual charged residues in the VSD (S1–S4) revealed that only the neutralization of two arginines in S4 (R210 and R213) changed the voltage dependence of the Q(V) curves. Neutralization of other VSD charges point to roles in tuning of the half-activation voltage of the VSD and its allosteric coupling with the PD. Molecular dynamics (MD) simulations based on the cryo-EM structures of the human BK channel (35) as templates suggested that R210 and R213 lie in a very narrow septum separating intra- and extracellular water-filled vestibules. This interpretation is consistent with the robust hyperpolarization-activated proton currents generated when R210 is mutated to the protonable amino acid histidine. Overall, our results point to a unique and distinctive mode of activation in BK: In contrast to Kv channels, where positive charges move one by one through a charge transfer center (absent in BK channels) that spans the entire electric field (36, 37), charge movement in BK channels is limited to the small displacement of R210 and R213, which itself constitutes a narrow septum where the electric field drops.     

COVID-19 vaccine-induced lymphadenopathies: incidence,course and imaging features from an ultrasound prospective study

Aimslymphadenopathy can occur after COVID-19 vaccination and when encountered at ultrasound examinations performed for other reasons might pose a diagnostic challenge. Purpose of the study was to evaluate the incidence, course and ultrasound imaging features of vaccine-induced lymphadenopathy.Methods89 healthy volunteers (median age 30, 76 females) were prospectively enrolled. Vaccine-related clinical side effects (e.g., fever, fatigue, palpable or painful lymphadenopathy) were recorded. Participants underwent bilateral axillary, supraclavicular and cervical lymph node stations ultrasound 1–4 weeks after the second dose and then again after 4–12 weeks in those who showed lymphadenopathy at the first ultrasound. B-mode, color-Doppler assessment, and shear-wave elastography (SWE) evaluation were performed. The correlation between lymphadenopathy and vaccine-related side effects was assessed using the Fisher’s exact test.ResultsPost-vaccine lymphadenopathy were found in 69/89 (78%) participants (37 single and 32 multiple lymphadenopathy). Among them, 60 presented vaccine-related side effects, but no statistically significant difference was observed between post-vaccine side effect and lymphadenopathy. Ultrasound features of vaccine-related lymphadenopathy consisted of absence of fatty hilum, round shape and diffuse or asymmetric cortical thickness (median cortical thickness of 5 mm). Vascular signal was mainly found to be increased, localized in both central and peripheral regions. SWE showed a soft cortical consistence in all cases (median value 11 Kpa). At follow-up, lymph-node morphology was completely restored in most cases (54/69, 78%) and in no case lymphadenopathy had worsened.ConclusionA high incidence of vaccine-induced lymphadenopathy was found in a population of healthy subjects, with nearly complete regression within 4–12 weeks.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40477-022-00674-3.