Laryngomalacia: a cause for early near miss for SIDS

Six infants had recurrent apnea of infancy episodes (near miss sudden infant death syndrome) during their neonatal period. Physical examination and laboratory investigation were normal. Polygraphic sleep monitoring revealed recurrent obstructive sleep apnea. These infants underwent fiberoptic endoscopy which showed that airway obstruction occurred at the laryngeal orifice as a result of laryngomalacia. It is suggested that laryngomalacia may be a cause for early apnea of infancy.     

Health of the elderly in a community in transition: a survey in Thiruvananthapuram City, Kerala, India

Results of a survey to assess the health and functional status of the elderly (defined as those who are 60 years or older) in Thiruvananthapuram city, the capital of Kerala state, India, are discussed. As the process of development results in longevity without concomitant economic success, traditional support systems break down. The differences in status of the elderly dependent on gender and socioeconomic class are highlighted. Women are poorer and generally suffer more morbidity than men in old age, even though their death rates are lower. The better-off among the elderly enjoy a quality of life much superior to their poor brethren. Thus, in transitional societies such as Kerala, socioeconomic status and gender play a significant role in determining the quality of life of the elderly, a finding which may have some policy implications.     

Low melatonin production in infants with a life-threatening event

This study compares the urinary excretion of the main melatonin metabolite, 6-sulfatoxymelatonin (6SMT), in infants who have and have not experienced a life-threatening event (ALTE). 6SMT was assessed in the following groups of infants: 15 infants with ALTE for whom home monitoring had been recommended, 15 infants who had had an abrupt cyanotic apneic event but did not require mouth-to-mouth resuscitation, 15 siblings of those who had died from sudden infant death syndrome (SIDS), and 35 age-matched healthy comparison infants. All 80 infants were between 48 and 58 weeks of postconceptional age. On a double-blind basis, the total amount of 6SMT excreted over 24 hours and the diurnal rhythm in the rate of 6SMT excretion were assessed using urine samples taken from disposable diapers (nappies). The mean daily excretion of 6SMT was significantly lower in the ALTE (1,588 ng/24 hour) than in the comparison infants (3,961 ng/24 hour). No such difference was found between the infants with a cyanotic apneic event (3,268 ng/24 hour) and the SIDS siblings (2,962 ng/24 hour). The diurnal 6SMT rhythms in the ALTE infants were characterized by lower 24-hour mean and amplitude values, whereas the time of peak and nadir excretion rates (07:15 to 08:45 hours and 14:45 to 16:15 hours respectively) was similar in all four infant groups. Follow-up of the ALTE infants, performed 6 to 8 weeks later (59 to 66 weeks of postconceptional age), revealed that 6SMT excretion increased in all of them, suggesting a delayed ontogeny rather than permanent deficiency of melatonin production in ALTE.     

Consistency of strength curves for determining maximal effort production during isokinetic knee testing of anterior cruciate ligament-deficient patients

The purpose of this investigation was to attempt to establish decision rules for determining maximal effort production during isokinetic strength testing of unilateral anterior cruciate ligament-deficient patients based on the degree of strength curve consistency within a set. Thirty-three participants performed six bilateral knee extension and flexion exertions at maximal effort and at 80% of perceived maximum at testing velocities of 60 and 180°s^–1. Within-set consistency was quantified by computation of the variance ratio across strength curves. Tolerance interval-based cutoff scores covering 99% of the population were calculated for declaring efforts as being maximal or not at confidence levels of 90%, 95%, and 99%. The sensitivity percentages attained for the injured knee for both testing velocities ranged between 9.1% and 27.2%, while specificity percentages ranged between 84.8% and 100%. For the non-injured knee, sensitivity values for both testing velocities ranged between 21.2% and 45.0%, while specificity percentages ranged between 97.0% and 100%. The developed decision rules do not effectively discriminate on an individual patient basis between maximal and non-maximal isokinetic knee musculature efforts. Further research is needed for development of methods that would enable to ascertain maximal effort production in this patient population during knee muscle strength testing.     

Maternal medical compromise during pregnancy and pregnancy outcomes

Objective: To examine the outcomes of pregnancy and newborn following an event of maternal medical compromise during pregnancy.

Methods: A retrospective study was performed on all patients hospitalized following an event of medical compromise during pregnancy. Medical compromise was divided to acute or chronic bleeding, major or complicated operations, and admission to intensive care unit (ICU). Data collected included maternal, fetal, neonatal and child’s follow-up.

Results: The study included 51 pregnant patients and 58 fetuses. The study group had increased risk of preterm deliveries (35.0 versus 6.5%, p?p?p?=?0.002). Patients with acute bleeding had higher rates of cesarean sections, preterm deliveries, admissions to neonatal ICU and neonatal mortality. Two cases of fetal abnormalities included brain abnormalities and pericardial effusion. Three terminations of pregnancies were performed: two in patients in ICU due to severe maternal medical condition and one in the fetus with brain abnormalities.

Conclusions: Maternal medical compromise during pregnancy increases the risk for preterm deliveries, cesarean delivery and low Apgar scores. Acute bleeding was the main cause of medical compromised and with the higher rates of adverse outcomes.     

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.     

Iron oxides stimulate sulfate-driven anaerobic methane oxidation in seeps

Seep sediments are dominated by intensive microbial sulfate reduction coupled to the anaerobic oxidation of methane (AOM). Through geochemical measurements of incubation experiments with methane seep sediments collected from Hydrate Ridge, we provide insight into the role of iron oxides in sulfate-driven AOM. Seep sediments incubated with ¹³C-labeled methane showed co-occurring sulfate reduction, AOM, and methanogenesis. The isotope fractionation factors for sulfur and oxygen isotopes in sulfate were about 40‰ and 22‰, respectively, reinforcing the difference between microbial sulfate reduction in methane seeps versus other sedimentary environments (for example, sulfur isotope fractionation above 60‰ in sulfate reduction coupled to organic carbon oxidation or in diffusive sedimentary sulfate–methane transition zone). The addition of hematite to these microcosm experiments resulted in significant microbial iron reduction as well as enhancing sulfate-driven AOM. The magnitude of the isotope fractionation of sulfur and oxygen isotopes in sulfate from these incubations was lowered by about 50%, indicating the involvement of iron oxides during sulfate reduction in methane seeps. The similar relative change between the oxygen versus sulfur isotopes of sulfate in all experiments (with and without hematite addition) suggests that oxidized forms of iron, naturally present in the sediment incubations, were involved in sulfate reduction, with hematite addition increasing the sulfate recycling or the activity of sulfur-cycling microorganisms by about 40%. These results highlight a role for natural iron oxides during bacterial sulfate reduction in methane seeps not only as nutrient but also as stimulator of sulfur recycling.Microbial dissimilatory processes generate energy through the decomposition of substrates, whereas assimilatory processes use substrates for intracellular biosynthesis of macromolecules. The most known and energetically favorable dissimilatory process is the oxidation of organic carbon coupled to oxygen as terminal electron acceptor (Eq. 1). In sediments with a high supply of organic carbon, oxygen can be depleted within the upper few millimeters, leading to anoxic conditions deeper in the sediment column. Under these conditions, microbial dissimilatory processes are coupled to the reduction of a series of other terminal electron acceptors besides oxygen (1). The largest free-energy yields are associated with nitrate reduction (denitrification), followed by manganese and iron oxide reduction, and then sulfate reduction. Due to the high concentration of sulfate in the ocean, dissimilatory bacterial sulfate reduction (Eq. 2) is responsible for the majority of organic matter oxidation in marine sediments (2). Below the depth of sulfate depletion, traditionally the only presumed process is methanogenesis (methane production), where its main pathways are fermentation of organic matter, mainly acetate (Eq. 3), or the reduction of carbon dioxide with hydrogen as substrate (Eq. 4) (3):O₂ + CH₂O → H₂O + CO₂[1]SO42−+2CH2O→H2S+2HCO3−[2]CH₃COOH→CH₄ + CO₂[3]CO₂ + 4H₂→CH₄ + 2H₂O[4]When methane that has been produced deep in sediments diffuses into contact with an available electron acceptor, it can be oxidized (methanotrophy). Methanotrophy is the main process that prevents the escape of methane produced within marine and fresh water sediments into the atmosphere. In fresh water systems, methanotrophic bacteria are responsible for oxidizing methane to dissolved inorganic carbon (DIC) typically using oxygen as an electron acceptor (4, 5). In marine sediments, however, where oxygen diffusion is limited, anaerobic oxidation of methane (AOM) coupled to sulfate reduction [e.g., refs. 6 and 7 (Eq. 5)] has been shown to consume up to 90% of the methane produced within the subseafloor environment (8). Often, when methane is present, the majority of sulfate available in marine pore fluids is reduced through sulfate-driven AOM (9–13):CH4+SO42−→HS−+HCO3−+H2O.[5]Other electron acceptors such as nitrate and oxides of iron and manganese, could also oxidize methane anaerobically and provide a greater free-energy yield than sulfate-coupled methane oxidation (14). Indeed, Beal et al. (15) showed the potential for iron- and manganese-driven AOM in microcosm experiments with methane seep sediments from Eel River Basin and Hydrate Ridge, and iron-driven AOM has been interpreted from modeling geochemical profiles in deep-sea sediments (13, 16). AOM has been shown to occur in nonmarine sediments via denitrification (17–21) and iron reduction (22, 23). However, all geochemical and microbiological studies point to sulfate-driven AOM as the dominant sink for methane in marine sediments.Sulfate-driven AOM is understood to involve microbial consortia of archaea and bacteria affiliated with archaeal methanotrophs (“methane oxidizers”) and sulfate-reducing bacteria (11, 24). A common view is that anaerobic methanotrophic archaea (ANME) oxidize methane, while the sulfate-reducing syntrophic partner scavenges the resulting reducing equivalents to reduce sulfate to sulfide (7, 25, 26). Recently, however, cultured AOM enrichments from seeps were reported to be capable of direct coupling of methane oxidation and sulfate reduction by the ANME-2 archaea, with the passage of zero valent sulfur to a disproportionating bacterial partner, capable of simultaneously oxidizing and reducing this substrate to sulfate and sulfide in a ratio of 1:7, respectively (27). Whether this “single organism mechanism” for sulfate-driven AOM is widespread in the natural environment, or whether there is a diversity of mechanisms for sulfate-driven AOM, remains enigmatic.Carbon isotopes provide a good constraint on the depth distribution and location of methanogenesis and methanotrophy because of the carbon isotope fractionation associated with these processes (e.g., refs. 28 and 29). During methanogenesis, ¹²C is strongly partitioned into methane; the δ¹³C of the methane produced can be between −50‰ to −110‰. In parallel, the residual DIC pool in methanogenic zones becomes highly enriched in ¹³C, occasionally by as much as 50‰ to 70‰ (e.g., ref. 28). Oxidizing this methane on the other hand, results in ¹³C-depleted DIC and slightly heavier δ¹³C values of the residual methane, caused by a fractionation of 0‰ to 10‰ during methane oxidation and the initial negative δ¹³C value of the methane itself (30, 31).The sulfur and oxygen isotopes in dissolved sulfate (δ³⁴S_SO4 and δ¹⁸O_SO4) may also be a diagnostic tool for tracking the pathways of sulfate reduction by methane or other organic compounds. Sulfur isotope fractionation during dissimilatory bacterial sulfate reduction, which partitions ³²S into the sulfide, leaving ³⁴S behind in the residual sulfate, can be as high as 72‰ (32–35). As sulfate is reduced to sulfide via intracellular intermediates (34, 36–40), the magnitude of this sulfur isotope fractionation depends upon the isotope partitioning at each of the intercellular steps and on the ratio between the backward and forward sulfur fluxes within the bacterial cells (34, 36).Oxygen isotopes in sulfate, however, have been shown to be strongly influenced by the oxygen isotope composition of water in which the bacteria are grown (41–45). The consensus is that, within the cell, sulfur compounds, such as sulfite, and water exchange oxygen atoms; some of these isotopically equilibrated molecules return to the extracellular sulfate pool. As all of the intercellular steps are considered to be reversible (e.g., refs. 34, 36, 46, and 47), water–oxygen is also incorporated during the oxidation of these sulfur intermediates back to sulfate (41–43, 48–51).Therefore, both oxygen and sulfur isotopes in the residual sulfate during dissimilatory sulfate reduction are affected by the changes in the intracellular fluxes of sulfur species. However, these isotopes in the residual sulfate are affected in different ways, and thus the change of one isotope vs. the other helps uniquely solve for the relative change in the flux of each intracellular step as sulfate is being reduced (42, 43, 50). The sulfur and oxygen isotope composition of residual sulfate has been used to explore the mechanism of traditional (organoclastic) sulfate reduction both in pure culture (e.g., refs. 44, 45, and 52) and in the natural environment (e.g., refs. 12, 49, 50, and 53–55). The coupled isotope approach has been used specifically to study sulfate-driven AOM recently in estuaries (56). In the work of Antler et al. (56), it was shown that the oxygen and sulfur isotopes in the residual sulfate in the pore fluids are linearly correlated during sulfate-driven AOM, whereas during organoclastic bacterial sulfate reduction, the isotopes exhibit a concaved curve relationship.Although iron and manganese oxides should be reduced before the onset of dissimilatory bacterial sulfate reduction in the natural environment from thermodynamic considerations, due to their low solubility, they may not be completely reduced through dissimilatory respiration when sulfate reduction starts (e.g., ref. 22). These lower reactivity manganese and iron oxides therefore may still be present during the lower-energy yielding anaerobic processes such as sulfate reduction, methanotrophy, and methanogenesis. Indeed, iron oxides have been shown to serve as electron acceptors for methane oxidation even in the sulfate “zone” (15, 16, 22, 57), although the mechanism of this coupling remains enigmatic. In the context of deep-sea methane seep ecosystems, earlier work by Beal et al. (15) demonstrated stimulation of AOM by the addition of iron and manganese oxides in sediment incubation experiments. In that work, however, the nature of the coupling between methane oxidation and metal oxides was not ascertained, and the multiple links between the sediment sulfur, iron, and methane cycles are equivocal.Here, we conducted microcosm experiments with sediments collected from Hydrate Ridge South (Fig. S1) and used synergistic combinations of isotope analyses (δ³⁴S_SO4, δ¹⁸O_SO4, and δ¹³C_DIC) to aid in assessing whether methane oxidation is directly coupled to the respiration of iron oxides or whether stimulation in methanotrophy is a result of the coupling between iron and sulfate. We provide compelling evidence for the stimulation of AOM in seep sediments through the coupling between iron and sulfate, and propose a mechanism for iron involvement in sulfate-driven AOM. Using microcosm experiments with seep sediments dominated by sulfate-driven AOM and amended with hematite and ¹³C-labeled methane and glucose, we are able to demonstrate the role of iron in sulfate-driven AOM. Hematite is a less reactive form of iron oxide than, for example, amorphous iron (58), and it was used to prevent the microbial populations from “switching” completely to the more energetically favorable process of iron reduction.     

Clinical and other specialty services offered by pharmacists in the community: the international arena and Israel

The community pharmacy setting is a venue that is readily accessible to the public. In addition, it is staffed by a pharmacist, who is a healthcare provider, trained and capable of delivering comprehensive pharmaceutical care. As such, community pharmacists have a colossal opportunity to serve as key contributors to patients’ health by ensuring appropriate use of medications, preventing medication misadventures, identifying drug-therapy needs, as well as by being involved in disease management, screening, and prevention programs. This unique position gives the pharmacist the privilege and duty to serve patients in roles other than solely that of the stereotypical drug dispenser.Worldwide, as well as in Israel, pharmacists already offer a variety of pharmaceutical services and tend to patients’ and the healthcare system’s needs. This article provides examples of professional, clinical or other specialty services offered by community pharmacists around the world and in Israel and describes these interventions as well as the evidence for their efficacy. Examples of such activities which were recently introduced to the Israeli pharmacy landscape due to legislative changes which expanded the pharmacist’s scope of practice include emergency supply of medications, pharmacists prescribing, and influenza vaccination. Despite the progress already made, further expansion of these opportunities is warranted but challenging. Independent prescribing, as practiced in the United Kingdom or collaborative drug therapy management programs, as practiced in the United States, expansion of vaccination programs, or wide-spread recognition and reimbursement for medication therapy management (MTM) programs are unrealized opportunities. Obstacles such as time constraints, lack of financial incentives, inadequate facilities and technology, and lack of professional buy-in, and suggested means for overcoming these challenges are also discussed.