Early postpartum hemorrhage after induction of labor

M.M., a 25‐year‐old Hispanic primigravida at 41 weeks and 6 days gestation, presented to the labor and delivery unit for postdates induction of labor, accompanied by the father of the baby. She reported normal fetal movement and denied any loss of fluid or vaginal bleeding. Her prenatal course was uncomplicated. The fetal heart rate was reassuring. Occasional contractions were recorded by the tocometer, but not felt by M.M. A pelvic exam found her cervix to be 1 cm dilated, 80% effaced, soft and posterior, with the vertex at ?2 station with membranes intact. Based on a Bishop score of 7, the decision was made to proceed with induction of labor with intravenous oxytocin per hospital protocol of 1 mU every 15 minutes to a maximum of 5 contractions in 10 minutes lasting no more than 60 to 90 seconds or a maximum dose of 20 mU/min. Three hours after oxytocin was initiated, M.M.'s cervical exam was 2 cm dilated, 80% effaced, with the vertex at ?2 station. The fetal heart rate baseline was 135 beats per minute with moderate variability and no decelerations. Six hours after admission, M.M. requested pain relief. Her cervical exam was 4 cm dilated, 90% effaced, with the vertex at ?1 station. The oxytocin was infusing at 16 mU/min and the fetal heart rate was reassuring. Pain management options were discussed with the client and, after being counseled on the risks and benefits, she opted for epidural anesthesia. Eight hours after admission, M.M.'s uterine contractions became difficult to detect with the external tocometer. At examination, her cervix was found to be 7 cm dilated, 100% effaced, with the vertex at 0 station. The oxytocin was infusing at 20 mU/min. The midwife counseled the client on the need to monitor uterine contractions when receiving oxytocin and the decision was made to rupture M.M's bag of waters and place an intrauterine pressure catheter. M.M.'s membranes were ruptured and it was noted that she had a moderate amount of clear amniotic fluid. The intrauterine pressure catheter was placed without complications and recorded adequate uterine contractions of 230 MvU. Eleven hours after admission, M.M. reported rectal pressure and a desire to push. Her cervix was examined and found to be fully dilated with the vertex at +2 station, and again the fetal heart rate was reassuring. Pushing efforts were commenced. One and a half hours later—12 and half hours after the initiation of induction—M.M. gave birth to a vigorous baby girl weighing 3000 g, with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively. The oxytocin infusion was discontinued immediately after delivery. Twenty‐five minutes later, the placenta was expelled spontaneously and appeared intact. An infusion of 20 units of oxytocin in 1000 cc of lactated ringers was given intravenously at 125 ml/hr. Fundal massage was started immediately after delivery of the placenta, because the uterine fundus was found to be boggy, and vaginal bleeding continued to increase. Bimanual uterine compression was added to control the hypotonic uterine bleeding. The urinary bladder was catheterized, producing 100 ml of urine. Ten units of oxytocin were administered intramuscularly in the thigh, again with poor response. Methylergonovine maleate 0.2 mg was then given intramuscularly. The obstetrician on call was notified of the client's uncontrolled immediate postpartum hemorrhage related to atony. Four minutes after Methergine administration, the fundus was firm and bleeding minimal. Twelve hours after delivery, M.M.'s hemoglobin (Hgb) and hematocrit (Hct) were noted to have decreased 23% from her levels at admission. Her Hgb was 7.8 g/dL, and she had an Hct of 23.9%. Her vital signs remained stable throughout, urine output satisfactory, and the client was able to tolerate walking without assistance.     

Immunomodulatory and anti-SARS activities of Houttuynia cordata

BACKGROUND: Severe acute respiratory syndrome (SARS) is a life-threatening form of pneumonia caused by SARS coronavirus (SARS-CoV). From late 2002 to mid 2003, it infected more than 8000 people worldwide, of which a majority of cases were found in China. Owing to the absence of definitive therapeutic Western medicines, Houttuynia cordata Thunb. (Saururaceae)(HC) was shortlisted by Chinese scientists to tackle SARS problem as it is conventionally used to treat pneumonia. AIM OF THE STUDY: The present study aimed to explore the SARS-preventing mechanisms of HC in the immunological and anti-viral aspects. RESULTS: Results showed that HC water extract could stimulate the proliferation of mouse splenic lymphocytes significantly and dose-dependently. By flow cytometry, it was revealed that HC increased the proportion of CD4(+) and CD8(+) T cells. Moreover, it caused a significant increase in the secretion of IL-2 and IL-10 by mouse splenic lymphocytes. In the anti-viral aspect, HC exhibited significant inhibitory effects on SARS-CoV 3C-like protease (3CL(pro)) and RNA-dependent RNA polymerase (RdRp). On the other hand, oral acute toxicity test demonstrated that HC was non-toxic to laboratory animals following oral administration at 16 g/kg. CONCLUSION: The results of this study provided scientific data to support the efficient and safe use of HC to combat SARS.     

The role of high-risk HPV-DNA testing in the male sexual partners of women with HPV-induced lesions

OBJECTIVES: The objectives were to assess the prevalence of high-risk HPV in the male sexual partners of women with HPV-induced lesions, and correlate it with biopsies guided by peniscopy. STUDY DESIGN: Fifty-four asymptomatic male sexual partners of women with low-grade squamous intra-epithelial lesions (LSIL) associated with high-risk HPV were examined between April 2003 and June 2005. The DNA-HPV was tested using a second-generation hybrid capture technique in scraped penile samples. Peniscopy identified acetowhite lesions leading to biopsy. RESULTS: High-risk HPV was present in 25.9% (14 out of 54) of the cases. Peniscopy led to 13 biopsies (24.07%), which resulted in two cases of condyloma, two cases of intra-epithelial neoplasia (PIN) I, one case of PIN II, and eight cases of normal tissue. The high-risk HPV test demonstrated 80% sensitivity, 100% specificity, 100% positive predictive value, and 88.9% negative predictive value for the identification of penile lesions. There was a greater chance of finding HPV lesions in the biopsy in the positive cases of high-risk HPV with abnormal peniscopy (p=0.007); OR=51 (CI 1.7-1527.1). CONCLUSION: Among asymptomatic male sexual partners of women with low-grade intra-epithelial squamous lesions, those infected by high-risk HPV have a higher chance of having abnormal penile tissue compared with male partners without that infection.     

Effects of Cadmium and Phenol on Motility and Ultrastructure of Sea Urchin and Mussel Spermatozoa

Computer-assisted sperm analysis (CASA) was used to study the effects of Cd(II) and phenol on sperm motility of sea urchin and mussel. In parallel, ultrastructural changes of sperm induced by these two toxicants were also investigated and related to motility impairment. Spermatozoa of sea urchin were more sensitive than mussel spermatozoa to both toxicants. Sea urchin sperm motility showed a good dose-response relationship to Cd(II) levels as well as exposure time. Exposure to the two toxicants changed the size and shape of the midpiece, which might affect the balance of spermatozoa in their swimming. The plasma membrane became more convoluted, and such a change might affect the streamlining and integrity of spermatozoa and hinder their normal movement patterns. Most important, disorganization of mitochondrial membranes and cristae was observed, suggesting disruption of ATP supply for sperm movement. Cadmium also induced greater ultrastructural damages in sea urchin spermatozoa. Received: 8 March 1999/Accepted: 29 September 1999     

Availability of Safe Childbirth Supplies in 284 Facilities in Uttar Pradesh,India

Maternal and Child Health Journal - Objectives Vital to implementation of the World Health Organization (WHO) Safe Childbirth Checklist (SCC), designed to improve delivery of 28 essential birth...     

Reduced H+ channel activity disrupts pH homeostasis and calcification in coccolithophores at low ocean pH

Coccolithophores are major producers of ocean biogenic calcite, but this process is predicted to be negatively affected by future ocean acidification scenarios. Since coccolithophores calcify intracellularly, the mechanisms through which changes in seawater carbonate chemistry affect calcification remain unclear. Here we show that voltage-gated H⁺ channels in the plasma membrane of Coccolithus braarudii serve to regulate pH and maintain calcification under normal conditions but have greatly reduced activity in cells acclimated to low pH. This disrupts intracellular pH homeostasis and impairs the ability of C. braarudii to remove H⁺ generated by the calcification process, leading to specific coccolith malformations. These coccolith malformations can be reproduced by pharmacological inhibition of H⁺ channels. Heavily calcified coccolithophore species such as C. braarudii, which make the major contribution to carbonate export to the deep ocean, have a large intracellular H⁺ load and are likely to be most vulnerable to future decreases in ocean pH.

Anthropogenic CO₂ emissions and the subsequent dissolution of CO₂ in seawater have resulted in substantial changes in ocean carbonate chemistry (1). The resultant decrease in seawater pH, termed ocean acidification, is predicted to be particularly detrimental for calcifying organisms (2). Mean global surface ocean pH is currently around 8.2 but is predicted to fall as low as 7.7 by 2100 (3) and is likely to continue to fall further in the following centuries. Present-day marine organisms can experience significant fluctuations in seawater pH, particularly in coastal and upwelling regions (4, 5). Ocean acidification is therefore predicted to have an important influence not only on mean surface ocean pH but also on the extremes of pH experienced by marine organisms (6, 7).Coccolithophores (Haptophyta) are a group of globally distributed unicellular phytoplankton that are characterized by their covering of intricately formed calcite scales (coccoliths). Coccolithophores account for a significant proportion of ocean productivity and are the main producers of biogenic calcite, making major contributions to global biogeochemical cycles, including the long-term export of both inorganic and organic carbon from the ocean photic zone to deep waters (8, 9). Unlike the vast majority of calcifying organisms, coccolithophore calcification occurs in an intracellular compartment, the Golgi-derived coccolith vesicle (CV), effectively isolating the calcification process from direct changes in seawater carbonate chemistry. Nevertheless, extensive laboratory observations indicate that ocean acidification may negatively impact coccolithophore calcification, albeit with significant variability of responses between species and strains (10–14). The negative impact on calcification rates occurs at calcite saturation states (Ω_calcite) >1, indicating that it results primarily from impaired cellular production rather than dissolution (10, 15). However, prediction of how natural coccolithophore populations may respond to future changes in ocean pH are hampered by lack of mechanistic understanding of pH impacts at the cellular level (10).As calcification occurs intracellularly using external HCO₃⁻ as the primary dissolved inorganic carbon (DIC) source (16–18), coccolith formation is not directly dependent on external CO₃²⁻ concentrations. However, the uptake of HCO₃⁻ as a substrate for calcification results in the equimolar production of CaCO₃ and H⁺ in the CV (18). In order to maintain saturation conditions for calcite formation, H⁺ produced by the calcification process must be rapidly removed from the CV, placing extraordinary demands for cellular pH regulation to prevent cellular acidosis (18).Lower calcification rates under ocean acidification conditions appear to be primarily due to decreased pH rather than other aspects of carbonate chemistry (10, 19, 20). Coccolithophores exhibit highly unusual membrane physiology, including the presence of voltage-gated H⁺ channels in the plasma membrane (21) and a high sensitivity of cytosolic pH (pH_cyt) to changes in external pH (pH_o) (21, 22). Voltage-gated H⁺ channels are associated with rapid H⁺ efflux in a number of specialized animal cell types (23) and contribute to effective pH regulation in coccolithophores (21). As H⁺ channel function is dependent on the electrochemical gradient of H⁺ across the plasma membrane, this mechanism could be impaired under lower seawater pH. However, it remains unknown whether H⁺ channels play a direct role in removal of calcification-derived H⁺ or contribute to the sensitivity of coccolithophores to ocean acidification.Coccolithophores exhibit significant diversity in their extent of calcification (SI Appendix, Fig. S1). The ratio of particulate inorganic carbon to particulate organic carbon (PIC/POC) of a coccolithophore culture is a measure of the relative rates of inorganic carbon fixation by calcification and organic carbon fixation by photosynthesis, respectively, and is commonly used as a simple metric to define the degree of calcification. The abundant bloom-forming species Emiliania huxleyi is moderately calcified (PIC/POC of around 1) and has been the focus of the vast majority of the studies into the effects of environmental change in coccolithophores (13). Coastal species belonging to the Pleurochrysidaceae and Hymenomonadaceae are lightly calcified, commonly exhibiting a PIC/POC of less than 0.5 (24–27). Species such as Coccolithus braarudii, Calcidiscus leptoporus, and Helicosphaera carteri exhibit much higher PIC/POC ratios and contribute the majority of carbonate export to the deep ocean in many areas (28–30). The physiological response of heavily calcified coccolithophores to ocean acidification is therefore of considerable biogeochemical significance. Growth and calcification rates in C. leptoporus and C. braarudii are sensitive to pH values predicted to prevail on a future decadal timescale (10, 15, 31, 32). However, a mechanistic understanding of the different sensitivity of coccolithophore species to changing ocean carbonate chemistry is lacking.The net H⁺ load in a cell is determined by the combination of metabolic processes that consume or produce H⁺. H⁺ fluxes in coccolithophores will be primarily determined by the balance of H⁺ consumed by photosynthesis and H⁺ generated by calcification, with uptake of different carbon sources a particularly important consideration (Fig. 1A). CO₂ uptake for photosynthesis results in no net production or consumption of H⁺, whereas uptake of HCO₃⁻ requires the equimolar consumption of H⁺ in order to generate CO₂. Growth at elevated CO₂ causes a switch from HCO₃⁻ uptake to predominately CO₂ uptake in E. huxleyi (33, 34). The associated net decrease in H⁺ consumption will therefore increase the H⁺ load in coccolithophores grown at elevated CO₂, which may exacerbate the potential for cytosolic acidosis caused by lower seawater pH.Open in a separate windowFig. 1.Physiology and H⁺ fluxes of C. braarudii cells grown at different seawater pH. (A) Schematic indicating H⁺ fluxes associated with photosynthesis and calcification in a coccolithophore cell. While many metabolic processes may contribute to the cellular H⁺ budget, these two processes are likely to be the major contributors. In a cell taking up HCO₃⁻, the overall H⁺ budget is determined by the relative rates of H⁺ consumed during photosynthesis and H⁺ generated during calcification. In a cell taking up CO₂, the H⁺ budget is determined primarily by calcification, as 2 H⁺ are produced for each molecule of CaCO₃ produced and H⁺ are no longer consumed during photosynthesis. In both scenarios, excess H⁺ may be removed from the cell by H⁺ transporters in the plasma membrane, such as voltage-gated H⁺ channels (H_v). Coccolithophores take up both HCO₃⁻ and CO₂ across the plasma membrane, with increasing proportions of DIC taken up as CO₂ as seawater CO₂ increases (34). (B) Growth rate of C. braarudii cells acclimated to different seawater pH. n = 3 replicates per treatment; line represents polynomial fit to mean. (C) Cellular production of POC through photosynthesis and PIC through calcification. The optima for both processes are close to the control conditions (pH 8.15). (D) As a consequence of the unequal changes in cellular POC and PIC production across the applied pH values, cellular PIC/POC ratios are minimal at pH 7.55 (∼1.0) and maximal at pH 8.45 (∼1.8). (E) Calculated net H⁺ budgets under the different pH regimes, based on rates of photosynthesis and calcification shown in C (see Materials and Methods). The concentration of CO₂ in seawater is also shown (dashed line). Estimates are shown for cells using taking up only HCO₃⁻ or only CO₂. As C. braarudii cells will likely take up a mixture of both DIC species, with a shift toward greater CO₂ usage at elevated CO₂, the shaded area represents the potential range of H⁺ production. Regardless of DIC species used C. braarudii produces excess H⁺ at all applied pH values, but H⁺ production is much lower at pH 7.55 due to the decrease in calcification.In this study we set out to better understand the cellular mechanisms underlying the sensitivity of coccolithophore calcification to lower pH. We subjected the heavily calcified species C. braarudii, which is commonly found in temperate upwelling regions (35, 36), to conditions that reflect the range of pH values it may experience in current and future oceans. We show that acclimation to low pH leads to loss of H⁺ channel function and disruption of cellular pH regulation in C. braarudii. These effects are coincident with very specific defects in coccolith morphology that can be reproduced by direct inhibition of H⁺ channels. We conclude that H⁺ efflux through H⁺ channels is essential for maintaining both calcification rate and coccolith morphology. By providing a mechanistic insight into pH regulation during the calcification process, our results indicate that disruption of coccolithophore calcification in a future acidified ocean is likely to be most severe in heavily calcified species.     

The seasonal relationships between household dietary diversity and child growth in a rural Timor‐Leste community

Both child growth and dietary diversity are poor in rural Timor‐Leste. The rainy season is associated with food scarcity, yet the association between seasonal scarcity, food diversity, and child growth is underdocumented. This study assesses the relationship between household dietary diversity and children''s standardized growth across the 2018 food‐scarce (April–May; post‐rainy period) and post‐harvest (October) seasons in the agricultural community of Natarbora, on the south‐coastal plains of Timor‐Leste. We conducted household interviews and collected anthropometric data across 98 and 93 households in the post‐rainy and post‐harvest periods, respectively. Consumed household foods were obtained via 24‐h diet recalls and were subsequently categorized into a nine‐food‐group dietary diversity score (DDS; number of different food groups consumed). The DDS was related to children''s standardized short‐term growth (z‐weight, z‐body mass index [BMI] and percent change in weight over the harvest season) via linear mixed models. Across seasons, DDS increased from 3.9 (standard deviation [SD] = 1.0) to 4.3 (SD = 1.4; p < 0.05). In the post‐rainy season, children in high DDS households had higher z‐weight than those in low DDS households and higher z‐BMI than children in medium and low DDS households. In the post‐harvest period, household DDS did not predict children''s z‐weight but predicted z‐BMI. Consumption of protein‐rich foods, particularly animal‐source foods and legumes, in low‐ and medium‐DDS households may be associated with improved child growth. While consuming more animal‐source foods in the post‐rainy season would be ideal, promoting the consumption of locally grown legumes, such as beans and pulses, may facilitate better nutritional outcomes for more children in rural Timor‐Leste.     

Evaluation of a Wastewater-Based Epidemiological Approach to Estimate the Prevalence of SARS-CoV-2 Infections and the Detection of Viral Variants in Disparate Oregon Communities at City and Neighborhood Scales

Background: Positive correlations have been reported between wastewater SARS-CoV-2 concentrations and a community’s burden of infection, disease or both. However, previous studies mostly compared wastewater to clinical case counts or nonrepresentative convenience samples, limiting their quantitative potential.Objectives: This study examined whether wastewater SARS-CoV-2 concentrations could provide better estimations for SARS-CoV-2 community prevalence than reported cases of COVID-19. In addition, this study tested whether wastewater-based epidemiology methods could identify neighborhood-level COVID-19 hotspots and SARS-CoV-2 variants.Methods: Community SARS-CoV-2 prevalence was estimated from eight randomized door-to-door nasal swab sampling events in six Oregon communities of disparate size, location, and demography over a 10-month period. Simultaneously, wastewater SARS-CoV-2 concentrations were quantified at each community’s wastewater treatment plant and from 22 Newport, Oregon, neighborhoods. SARS-CoV-2 RNA was sequenced from all positive wastewater and nasal swab samples. Clinically reported case counts were obtained from the Oregon Health Authority.Results: Estimated community SARS-CoV-2 prevalence ranged from 8 to 1,687/10,000 persons. Community wastewater SARS-CoV-2 concentrations ranged from 2.9 to 5.1log10 gene copies per liter. Wastewater SARS-CoV-2 concentrations were more highly correlated (Pearson’s r=0.96; R2=0.91) with community prevalence than were clinically reported cases of COVID-19 (Pearson’s r=0.85; R2=0.73). Monte Carlo simulations indicated that wastewater SARS-CoV-2 concentrations were significantly better than clinically reported cases at estimating prevalence (p<0.05). In addition, wastewater analyses determined neighborhood-level COVID-19 hot spots and identified SARS-CoV-2 variants (B.1 and B.1.399) at the neighborhood and city scales.Discussion: The greater reliability of wastewater SARS-CoV-2 concentrations over clinically reported case counts was likely due to systematic biases that affect reported case counts, including variations in access to testing and underreporting of asymptomatic cases. With these advantages, combined with scalability and low costs, wastewater-based epidemiology can be a key component in public health surveillance of COVID-19 and other communicable infections. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10289","term_id":"372009674","term_text":"EHP10289"}}EHP10289     

New frontiers of retinal therapeutic intervention: a critical analysis of novel approaches

A recent wave of pharmacologic and technologic innovations has revolutionized our management of retinal diseases. Many of these advancements have demonstrated efficacy and can increase the quality of life while potentially reducing complications and decreasing the burden of care for patients. Some advances, such as longer-acting anti-vascular endothelial growth factor agents, port delivery systems, gene therapy, and retinal prosthetics have been approved by the US Food and Drug Administration, and are available for clinical use. Countless other therapeutics are in various stages of development, promising a bright future for further improvements in the management of the retinal disease. Herein, we have highlighted several important novel therapies and therapeutic approaches and examine the opportunities and limitations offered by these innovations at the new frontier.

KEY MESSAGES

• Numerous pharmacologic and technologic advancements have been emerging, providing a higher treatment efficacy while decreasing the burden and associated side effects.
• Anti-vascular endothelial growth factor (anti-VEGF) and its longer-acting agents have dramatically improved visual outcomes and have become a mainstay treatment in various retinal diseases.
• Gene therapy and retinal prosthesis implantation in the treatment of congenital retinal dystrophy can accomplish the partial restoration of vision and improved daily function in patients with blindness, an unprecedented success in the field of retina.