Erratum to: Blueberry Supplementation Effects on Neuronal and Pathological Biomarkers in Subjects at Risk for Alzheimer's Disease: A Pilot Study.

[This corrects the article DOI: 10.14283/jarlife.2023.13.].

Blueberry Supplementation Effects on Neuronal and Pathological Biomarkers in Subjects at Risk for Alzheimer's Disease: A Pilot Study.

Background: There is a need to develop non-invasive practical lifestyle interventions for preventing Alzheimer's disease (AD) in people at risk, such as those with mild cognitive impairment (MCI). Blueberry consumption has been associated with reduced risk of dementia in some epidemiologic studies and with improvements in cognition in healthy aging adults. Blood-based biomarkers have emerged at the forefront of AD therapeutics research spurred by the development of reliable ultra-sensitive "single-molecule array" assays with 100-1000-fold greater sensitivity over traditional platforms. Objective: The purpose of this study was to examine the effect of blueberry supplementation in MCI on six blood biomarkers: amyloid-beta 40 (Aß40), amyloid-beta 42 (Aß42), phosphorylated Tau181 (ptau181), neurofilament light (NfL), Glial Fibrillary acidic protein (GFAP), and Brain-Derived Neurotrophic Factor (BDNF). Methods: This was a 12-week, open-label, pilot trial of 10 participants with MCI (mean age 80.2 years + 5.16). Subjects consumed 36 grams per day of lyophilized blueberry powder in a split dose consumed with breakfast and dinner. Baseline and endpoint venous blood was analyzed using an ultrasensitive SIMOA assay. Our aim was to test if blueberry supplementation would particularly impact p-tau181, NfL, and GFAP elevations associated with the neurodegenerative process. Results: There were no statistically significant (p < 0.05) changes from baseline to endpoint for any of the biomarker values or in the ratios of Aß42 / Aß40 and ptau181/ Aß42. Adverse effects were mild and transient; supplementation was relatively well tolerated with all subjects completing the study. Conclusion: To our knowledge, this is the first study to prospectively examine the effects of blueberry supplementation on a panel of blood biomarkers reflecting the neurodegenerative process. Our findings raise two possibilities - a potential stabilization of the neurodegenerative process or a lack of a direct and acute effect on beta-amyloid/tau/glial markers. A larger controlled study is warranted.

Outcomes of patients with COVID-19 acute respiratory distress syndrome requiring invasive mechanical ventilation admitted to an intensive care unit in South Africa.

BACKGROUND: Up to 32% of patients with COVID-19 pneumonia may require intensive care unit (ICU) admission or mechanical ventilation. Data from low- and middle-income countries on COVID-19 acute respiratory distress syndrome (ARDS) are limited. Groote Schuur Hospital in Cape Town, South Africa, expanded its intensive care service to support patients with COVID-19 ARDS requiring invasive mechanical ventilation (IMV). OBJECTIVES: To report on patients' characteristics and outcomes from the first two pandemic waves. METHODS: All patients with COVID-19 ARDS admitted to the ICU for IMV were included in this prospective cohort study. Data were collected from 5 April 2020 to 5 April 2021. RESULTS: Over the 12-month study period, 461 patients were admitted to the designated COVID-19 ICU. Of these, 380 met the study criteria and 377 had confirmed hospital discharge outcomes. The median (range) age of patients was 51 (17 - 71) years, 50.5% were female, and the median (interquartile range (IQR)) body mass index was 32 (28 - 38) kg/m2. The median (IQR) arterial oxygen partial pressure to fractional inspired oxygen (P/F) ratio was 97 (71 - 128) after IMV was initiated. Comorbidities included diabetes (47.6%), hypertension (46.3%) and HIV infection (10.5%). Of the patients admitted, 30.8% survived to hospital discharge with a median (IQR) ICU length of stay of 19.5 (9 - 36) days. Predictors of mortality after adjusting for confounders were male sex (odds ratio (OR) 1.74), increasing age (OR 1.04) and higher Sequential Organ Failure Assessment (SOFA) score (OR 1.29). CONCLUSIONS: In a resource-limited environment, the provision of IMV support in the ICU achieved 30.8% hospital survival in patients with COVID-19 ARDS. The ability to predict survival remains difficult given this complex disease.

The organisational response of a hospital critical care service to the COVID-19 pandemic: The Groote Schuur Hospital experience.

Background: There are limited data about the coronavirus disease-19 (COVID-19)-related organisational responses and the challenges of expanding a critical care service in a resource-limited setting. Objectives: To describe the ICU organisational response to the pandemic and the main outcomes of the intensive care service of a large state teaching hospital in South Africa. Methods: Data were extracted from administrative records and a prospective patient database with ethical approval. An ICU expansion plan was developed, and resource constraints identified. A triage tool was distributed to referring wards and hospitals. Intensive care was reserved for patients who required invasive mechanical ventilation (IMV). The total number of ICU beds was increased from 25 to 54 at peak periods, with additional non-COVID ICU capacity required during the second wave. The availability of nursing staff was the main factor limiting expansion. A ward-based high flow nasal oxygen (HFNO) service reduced the need for ICU admission of patients who failed conventional oxygen therapy. A team was established to intubate and transfer patients requiring ICU admission but was only available for the first wave. Results: We admitted 461 COVID-19 patients to the ICU over a 13-month period from 5 April 2020 to 5 May 2021 spanning two waves of admissions. The median age was 50 years and duration of ICU stay was 9 days. More than a third of the patients (35%; n=161) survived to hospital discharge. Conclusion: Pre-planning, leadership, teamwork, flexibility and good communication were essential elements for an effective response. A shortage of nurses was the main constraint on ICU expansion. HFNO may have reduced the requirement for ICU admission, but patients intubated after failing HFNO had a poor prognosis. Contributions of the study: We describe the organisational requirements to successfully expand critical care facilities and strategies to reduce the need for invasive mechanical ventilation in COVID-19 pneumonia. We also present the intensive care outcomes of these patients in a resource-constrained environment.

Carbohydrate loading in the preoperative setting.

Nutrition support is an evolving field, and modern clinical nutrition practice should actively incorporate strategies to enhance various clinical outcomes. In surgical patients, clinical benefits can be maximised by nutritional support protocols that minimise and manage the perioperative fasting period. This approach, which includes the perioperative provision of clear carbohydrate-containing fluids, has been shown to be safe, is evidence based, and is supported by many professional societies. Such a strategy has been shown to aid the anaesthetic process and maintain an optimal metabolic state, including improved insulin sensitivity and blunted muscle catabolic activity. Some important consequences of this improved metabolic control include shorter hospital stay and fewer postoperative complications. A proactive multidisciplinary team approach is essential to use this nutrition support strategy with success across a hospital's surgical service.

Does early morning versus late morning draw time influence apparent testosterone concentration in men aged > or =45 years? Data from the Hypogonadism In Males study.

The Hypogonadism In Males study estimated the prevalence of hypogonadism in men aged > or =45 years. A sub-analysis of patients not receiving testosterone (T) therapy was conducted. Blood draw times were 0800-1000 and 1000-1200 hours. Total T (TT) was not influenced by draw time for any age group; however, significantly greater free T (FT) and bioavailable T (BAT) values were observed in the overall population for earlier draw times. Sex hormone-binding globulin (SHBG) values were significantly lower in men aged 45-64 years at the earlier draw time. In men aged > or =75 years, no significant differences in TT, FT, BAT or SHBG were observed on the basis of draw time. Early morning draw time may not be critical for capturing TT concentrations in men > or =45 years; however, when measuring FT or BAT, an early morning draw time may be preferable for men aged <75 years.

Intra-Abdominal Hypertension and the Abdominal Compartment Syndrome

The phenomenon of intra-abdominal hypertension (IAH) and its progression to abdominal compartment syndrome (ACS) is a common and frequently under-recognised condition in critically ill patients. IAH is defined as an intra-abdominal pressure (IAP) greater than 12 mmHg. The ACS occurs once IAH is associated with organ dysfunction. Early detection is the cornerstone of management in the critically ill patient and the regular measurement of IAP in patients at risk for developing raised IAP is encouraged. The intravesical technique of measurement is relatively non-invasive and provides excellent correlation with direct measurement of IAP. The consequences of ACS are multi-systemic; resulting in organ dysfunction. The respiratory; cardiovascular; renal and gastrointestinal systems are particularly affected. The vicious cycle of organ dysfunction may be perpetuated by excessive fluid resuscitation. Early intervention is essential to prevent complications; which carry significant morbidity and; if untreated; possible mortality. Definitive management of this condition is the prompt surgical decompression of the abdomen followed by temporary abdominal closure

Stage-specific effects of the fungicide carbendazim on Sertoli cell microtubules in rat testis.

The aim of the present study is to provide a morphological explanation of carbendazim (CBZ)-induced sloughing of germ cells that occurs in a stage-specific manner. Therefore, very early alterations in the seminiferous tubule epithelium were examined histologically in the rat testis after oral administration of CBZ (400mg/kg). Gaps between the elongated and round spermatids, the first indication of germ cell sloughing (pre-sloughing), were observed in stage late VI-early VII seminiferous tubules at 90-min post-treatment. Tubulin immunoreaction in the Sertoli cells was reduced in intensity in tubules with pre-sloughing. However, electron microscopy demonstrated that there were some intact microtubules in these cells. At 120 min, sloughing was seen in stage late VI-early VII and XIII-XIV. Tubulin immunoreaction in the Sertoli cells was greatly decreased in intensity in tubules where cell sloughing was observed. Electron microscopy showed that there were few microtubules in the body region of these cells. Stages II-V and mid-VII-VIII were exempt from the sloughing effect at 180 min. These changes in microtubules were not observed in Sertoli cells that did not exhibit sloughing characteristics, regardless of the post-treatment intervals. The present results suggest that stage specificity of sloughing is due to the stage-specific susceptibility of Sertoli cell microtubules to CBZ.

alpha-Chlorohydrin inhibits glyceraldehyde-3-phosphate dehydrogenase in multiple organs as well as in sperm.

Numerous studies have documented inhibitory effects of alpha-chlorohydrin (ACH) on glyceraldehyde-3-phosphate dehydrogenase (G3PDH) activity in spermatozoa. A sperm-specific G3PDH isoform has been described. The possibility that ACH may inhibit G3PDH in cell types other than sperm was investigated in this work. In addition, the onset of ACH-induced epididymal toxicity was described. Changes to epididymal histology occurred 6 h following a single dose of ACH (50 mg/kg po) and were confined to the proximal initial segment. By 24 h, no epithelial cells lined the basement membrane of that region. Three h after ACH administration (50 mg/kg po), G3PDH activity was significantly decreased in sperm (85%) as well as in kidney (31%), liver (49%), and epididymis (35%). Enzyme activity remained inhibited at 6 and 24 h. G3PDH was immunolocalized in the epididymis and staining was highest in the efferent ducts and initial segment as well as in smooth muscle. Since G3PDH is a microtubule-associated protein and microtubule-dependent endocytosis occurs in the epididymis, beta-tubulin was also immunolocalized. beta-tubulin densely stained the apical region of initial segment and caput epithelial cells. Disruption of beta-tubulin immunostaining correlated with the localization and onset of the lesion. Co-localization of G3PDH and beta-tubulin immunostaining was not observed although both antibodies most densely stained the initial segment. Our data indicate that histologic changes to the proximal initial segment of the epididymis occur rapidly, but subsequent to G3PDH inhibition. Moreover, ACH inhibition of G3PDH is not confined to sperm, although the sperm enzyme is most sensitive to inhibition.

Microtubule depolymerization in rat seminiferous epithelium is associated with diminished tyrosination of alpha-tubulin.

In the testis, microtubule-disrupting agents cause breakdown of the Sertoli cell cytoskeleton and sloughing of germ cells with associated Sertoli cell fragments, although the mechanism underlying this event is not understood. In this study, we investigated the effects of carbendazim and colchicine on microtubule polymerization status and posttranslational modifications of tubulin in freshly isolated rat seminiferous tubules. Soluble and polymerized tubulin pools were separated and tubulin was quantified using a competitive ELISA. Carbendazim and colchicine caused extensive microtubule depolymerization, shifting the ratio of soluble to polymerized tubulin from 40%:60% to 78%:22%, and to 84%:16%, respectively. Total tubulin levels remained relatively constant after carbendazim treatment but decreased twofold after colchicine treatment. To determine if modifications to tubulin may be associated with polymerization status, tubulin pools were analyzed by immunoblotting. Acetylated alpha-tubulin and betaIII-tubulin distribution in tubulin pools was not affected by treatment. Tyrosinated alpha-tubulin (52 kDa) was localized in both tubulin pools and had decreased tyrosination in the microtubule pool after carbendazim treatment. A 47-kDa protein immunoreactive with both tyrosinated alpha-tubulin and general alpha-tubulin antibodies was found only in the microtubule pool. The 47-kDa protein (potentially an alpha-tubulin isoform) lost tyrosination, yet was still present in the microtubule pool based on detection with the general alpha-tubulin antibody, after carbendazim treatment. Similar effects were seen with colchicine, although loss of total tubulin protein was measured. Thus, decreased tyrosination of the microtubule pool of tubulin appears to be associated with depolymerization of microtubules.

alpha-chlorohydrin induced changes in sperm fertilizing ability in the rat: association with diminished sperm ATP levels and motility.

In the present study, alpha-chlorohydrin (ACH) (5, 10, 25, 50 and 75 mg/kg, po) was administered to rats and the effects on sperm ATP levels, sperm motility, and the ability of sperm to bind and penetrate rat oocytes were determined. Groups of rats were killed 5 days and 3 h following treatment. At both time points, sperm from ACH-treated rats (>/=10 mg/kg) had significantly lower levels of ATP when diluted in media containing glucose. No diminution of ATP was seen in sperm diluted in phosphate-buffered saline (PBS). Computer analysis of sperm motility indicated that straight-line velocity (VSL) was the most sensitive parameter to ACH treatment and was significantly decreased in rat sperm three hours after ACH exposure (25 mg/kg). A clear drop in percent penetration (35% vs. 85% in control) of zona-free rat oocytes by rat sperm of both ACH groups was observed at 10 mg/kg. Higher dose levels produced no significant further decrease in percent penetration. Overall, the fertilizing ability of sperm was highly sensitive to ACH doses that caused minor but significant changes in sperm ATP levels and no significant changes in motility. These data are consistent with the spermatozoan's need for an uncompromised energy supply to maintain its ability to bind and penetrate the oocyte.

Fluorescent probes and flow cytometry to assess rat sperm integrity and mitochondrial function.

Fluorescent assessment of cellular integrity and mitochondrial function by flow cytometry can provide a rapid and precise means of determining the functional status of large numbers of spermatozoa. In the present study, rat sperm viability was assessed with SYBR-14 and PI and sperm mitochondria were differentially labeled with JC-1. Sperm samples of variable viability were prepared using varying proportions of fresh and frozen spermatozoa. SYBR-14 stained sperm correlated well with expected sperm viability (r = 0.98). Motile sperm stained with JC-1 appeared orange in the midpiece indicating a high mitochondrial membrane potential whereas immotile sperm with a low membrane potential stained green. The percentage of spermatozoa staining orange was highly correlated (r = 0.99) with expected sperm viability. Flow cytometry using specific fluorescent probes is a useful technique for detecting changes in rat sperm plasma membrane integrity and mitochondrial function in large numbers of spermatozoa.

The role of GTP Binding and microtubule-associated proteins in the inhibition of microtubule assembly by carbendazim.

The fungicide carbendazim (CBZ) is known to disrupt microtubular structures in the testis and to cause testicular toxicity in rats. To investigate the mechanism underlying the toxicity of CBZ, tubulin and microtubule-associated proteins (MAPs) were isolated from rat testis and brain using two techniques. The effects of CBZ on MT assembly were compared with the known microtubule (MT) disruptors, colchicine and nocodazole. CBZ (100 microM) had no effect on the assembly of MTs from MAP-containing tubulin isolated with one cycle of glycerol-dependent assembly and disassembly while colchicine (40 microM) and nocodazole (12.5 microM) strongly inhibited the assembly reaction. Similarly, formation of MTs from tubulin prepared with two cycles of glycerol-dependent assembly was strongly inhibited by colchicine and nocodazole but only weakly by CBZ. All three compounds inhibited the assembly of MTs from MAP-free tubulin isolated with glutamate. However, the inhibition by CBZ was reversed by the inclusion of high-molecular-weight MAPs and not by unrelated protein (bovine serum albumin, BSA). Addition of nocodazole to assembled MTs caused immediate depolymerization, whereas CBZ did not directly cause depolymerization. However CBZ was an effective inhibitor of the polymerization of depolymerized tubulin. In competitive binding assays, CBZ was found to inhibit the binding of guanosine triphosphate (GTP) to tubulin. The data suggest that CBZ interferes with initial events of MT polymerization, specifically GTP binding, and that MAPs moderate this effect.

Virtual seminars for medical nutrition education: case example.

Nutrition educators are exploring Web-based strategies for delivering course material. This report describes an effort to use computer-mediated communication between medical students and experts. A "virtual seminar" designed to help students apply nutrition knowledge to patient care was added to an existing traditional clinical skills course. There are few models for online nutrition education. Since these efforts are expensive in time, money, or both, it is important to share preliminary findings, including new methods of evaluating participation and effectiveness. Although medical student activity in the seminar was greater than anticipated, the return rate for the online evaluation survey was disappointing.

Health-related physical fitness knowledge of student allied health professions.

Each allied-health profession has their own particular expertise but also shares some commonalities. One such commonality should be knowledge of health-related physical fitness relating to the health and well-being of individuals. Although the benefits of health-related physical fitness have been well documented, few studies have examined the level of health-related physical fitness knowledge among allied-health professions. Therefore, the purpose of this investigation was to assess the health-related physical fitness knowledge of three allied health professions using a 40 item multiple-choice test designed to assess knowledge in five domains of health-related physical fitness. Results indicated that student athletic trainers scored significantly higher on the post-test versus pre-test. On the post-test, athletic training and physical therapy groups scored significantly higher than the nursing group. The information from this study may be valuable in aiding educators in developing appropriate curricula to better prepare students for their role as allied health professionals.

In vitro fertilization after in vivo treatment of rats with three reproductive toxicants.

One objective of these experiments was to establish a sensitive assay to evaluate fertilizing potential of rat gametes in vitro. A second objective was to evaluate this in vitro fertilization (IVF) assay as a method to detect in vivo effects of reproductive toxicants on male and female gametes using three known reproductive toxicants as model systems. The IVF assay with zona-free oocytes was more precise than the assay with cumulus-intact oocytes in these studies (coefficients of variation of 8.7 and 14.4%, respectively). Sperm fertilizing potential for zona-free oocytes was reduced by treatment of rats with m-dinitrobenzene (10-10 000 microg/kg) and ethylene glycol monomethyl ether (50-100 mg/kg) that had no effect on sperm motility. Molinate (60 mg/kg for 5 days) reduced sperm fertilizing potential concurrently with reductions in sperm motility. Neither molinate (60 mg/kg for 5 days) nor dinitrobenzene (0.002% in the drinking water for 14 days) administered to females seemed to affect the fertilizability of their oocytes. Ethylene glycol monomethyl ether treatment (0.15-0.25% in the drinking water for 14 days) reduced the number of ovulated oocytes. IVF is a means to evaluate toxicant effects on female gametes and demonstrates sperm's ability to interact with the oocyte plasma membrane.

Continuous subcutaneous infusion of morphine vs. hydromorphone: a controlled trial.

Seventy-four patients were included in a double-blind, randomized, controlled trial comparing the analgesic efficacy and adverse effects of hydromorphone and morphine delivered by continuous subcutaneous infusion. Patients completed the Memorial Pain Assessment Card and a checklist of opioid-related adverse effects immediately before commencing subcutaneous infusion and 24, 48, and 72 hours later. An assessment tool was developed for the 60 patients who were too ill to complete their own questionnaire. The tool demonstrated excellent inter-rater reliability. Thirty-four percent of patients in the hydromorphone group and 27% of those in the morphine group died before completion of the study (P = 0.66). The hydromorphone group required more analgesia for breakthrough pain in the first 24 hours of the study (P = 0.03) and had a greater improvement in the behavior of frowning on movement and the comfort visual analogue scale (P = 0.08) over the course of the study. Adverse effects were rare and similar in both groups. This study found hydromorphone to be at least as effective as morphine when delivered by continuous subcutaneous infusion.