This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Host genetic factors are known to modify the susceptibility, severity, and outcomes of COVID-19 and vary across populations. However, continental Africans are yet to be adequately represented in such studies despite the importance of genetic factors in understanding Africa’s response to the pandemic. We describe the development of a research resource for coronavirus host genomics studies in South Africa known as COVIGen-SA—a multicollaborator strategic partnership designed to provide harmonised demographic, clinical, and genetic information specific to Black South Africans with COVID-19. Over 2,000 participants have been recruited to date. Preliminary results on 1,354 SARS-CoV-2 positive participants from four participating studies showed that 64.7% were female, 333 had severe disease, and 329 were people living with HIV. Through this resource, we aim to provide insights into host genetic factors relevant to African-ancestry populations, using both genome-wide association testing and targeted sequencing of important genomic loci. This project will promote and enhance partnerships, build skills, and develop resources needed to address the COVID-19 burden and associated risk factors in South African communities.

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.

The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.

The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

This study provides a morphological and phylogenetic characterization of two novel species of the order Haplosporida (Haplosporidium carcini n. sp., and H. cranc n. sp.) infecting the common shore crab Carcinus maenas collected at one location in Swansea Bay, South Wales, UK. Both parasites were observed in the haemolymph, gills and hepatopancreas. The prevalence of clinical infections (i.e. parasites seen directly in fresh haemolymph preparations) was low, at ~1%, whereas subclinical levels, detected by polymerase chain reaction, were slightly higher at ~2%. Although no spores were found in any of the infected crabs examined histologically (n = 334), the morphology of monokaryotic and dikaryotic unicellular stages of the parasites enabled differentiation between the two new species. Phylogenetic analyses of the new species based on the small subunit (SSU) rDNA gene placed H. cranc in a clade of otherwise uncharacterized environmental sequences from marine samples, and H. carcini in a clade with other crustacean-associated lineages.

OBJECTIVES/SPECIFIC AIMS: Background: Delirium is a well described form of acute brain organ dysfunction characterized by decreased or increased movement, changes in attention and concentration as well as perceptual disturbances (i.e., hallucinations) and delusions. Catatonia, a neuropsychiatric syndrome traditionally described in patients with severe psychiatric illness, can present as phenotypically similar to delirium and is characterized by increased, decreased and/or abnormal movements, staring, rigidity, and mutism. Delirium and catatonia can co-occur in the setting of medical illness, but no studies have explored this relationship by age. Our objective was to assess whether advancing age and the presence of catatonia are associated with delirium. METHODS/STUDY POPULATION: Methods: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Measures of association (OR) were assessed with a simple logistic regression model with catatonia as the independent variable and delirium as the dependent variable. Effect measure modification by age was assessed using a Likelihood ratio test. RESULTS/ANTICIPATED RESULTS: Results: We enrolled 136 medical and surgical critically ill patients with 452 matched (concomitant) delirium and catatonia assessments. Median age was 59 years (IQR: 52–68). In our cohort of 136 patients, 58 patients (43%) had delirium only, 4 (3%) had catatonia only, 42 (31%) had both delirium and catatonia, and 32 (24%) had neither. Age was significantly associated with prevalent delirium (i.e., increasing age associated with decreased risk for delirium) (p=0.04) after adjusting for catatonia severity. Catatonia was significantly associated with prevalent delirium (p<0.0001) after adjusting for age. Peak delirium risk was for patients aged 55 years with 3 or more catatonic signs, who had 53.4 times the odds of delirium (95% CI: 16.06, 176.75) than those with no catatonic signs. Patients 70 years and older with 3 or more catatonia features had half this risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Catatonia is significantly associated with prevalent delirium even after controlling for age. These data support an inverted U-shape risk of delirium after adjusting for catatonia. This relationship and its clinical ramifications need to be examined in a larger sample, including patients with dementia. Additionally, we need to assess which acute brain syndrome (delirium or catatonia) develops first.

3D printing has been shown to be a robust and inexpensive manufacturing tool for a range of applications within biomedical science. Here we report the design and fabrication of a 3D printer-enabled microfluidic device used to generate cell-laden hydrogel microspheres of tunable sizes. An inverse mold was printed using a 3D printer, and replica molding was used to fabricate a PDMS microfluidic device. Intersecting channel geometry was used to generate perfluorodecalin oil-coated gelatin methacrylate (GelMA) microspheres of varying sizes (35–250 μm diameters). Process parameters such as viscosity profile and UV cross-linking times were determined for a range of GelMA concentrations (7–15% w/v). Empirical relationships between flow rates of GelMA and oil phases, microspheres size, and associated swelling properties were determined. For cell experiments, GelMA was mixed with human osteosarcoma Saos-2 cells, to generate cell-laden GelMA microspheres with high long-term viability. This simple, inexpensive method does not require the use of traditional cleanroom facilities and when combined with the appropriate flow setup is robust enough to yield tunable cell-laden hydrogel microspheres for potential tissue engineering applications.

Metolachlor has been evaluated both as a herbicide for use in cultivated oats (Avena sativa L.) and for its potential as an alternative herbicide for the control of herbicide-resistant rigid ryegrass. Eight herbicide-resistant and two susceptible biotypes of rigid ryegrass were tested for their susceptibility to metolachlor. Response to metolachlor was determined both in soil and an agar germination medium. The LD50 for metolachlor in agar for a susceptible biotype (VLR1) was 0.13 μM. Five biotypes, SLR5 (6.9 fold), SLR31 (5.2 fold), SLR10 (2.5 fold), NLR12 (2.1 fold) and VLR69 (1.9 fold), were cross-resistant to metolachlor when compared with VLR1. Relative response of the biotypes was similar in both soil and agar, validating the use of an agar germination test to determine the susceptibility of rigid ryegrass biotypes to metolachlor. Biotypes cross-resistant to metolachlor also were cross-resistant to alachlor (SLR5 6.7 fold, SLR31 5.9 fold, SLR10 2.4 fold, and VLR69 1.6 fold with the LD50 for VLR1 being 0.49 μM) and propachlor (SLR57.2 fold, SLR31 7.2 fold, SLR10 3.0 fold and VLR69 2.5 fold with the LD50 for VLR1 being 0.47 μM) indicating that cross-resistance extends to other members of the chloroacetamide group. Cross-resistance to chloroacetamides was observed in biotypes that previously had been reported as cross-resistant to other herbicides. In contrast, biotypes with limited herbicide histories were generally not cross-resistant to metolachlor. These results indicate that there is a high probability of chloroacetamide cross-resistance in populations of herbicide-resistant rigid ryegrass.

Greenhouse studies were conducted to determine the response of common lambsquarters and velvetleaf to glyphosate applied alone or with 20 g L−1 of ammonium sulfate (AMS). Minimal response of common lambsquarters to glyphosate plus AMS was observed. The GR50 values for velvetleaf decreased dramatically from 451 to 92 g ha−1 for glyphosate applied alone and glyphosate plus AMS, respectively. The addition of AMS did not affect foliar absorption of 14C-glyphosate in common lambsquarters but increased absorption in velvetleaf. A twofold increase in translocation, as a percentage of total 14C-glyphosate absorbed, occurred in velvetleaf with the addition of AMS. Increased control of velvetleaf with glyphosate plus AMS may be partially explained by greater glyphosate absorption and translocation. Increased translocation of glyphosate applied with AMS in velvetleaf was an indirect effect of greater foliar uptake as well as greater partitioning of glyphosate out of the treated leaf.

A field trial was conducted for 6 yr (1998 through 2003) at Scottsbluff, NE, to measure weed shifts following multiple applications of two rates of glyphosate or alternating glyphosate with nonglyphosate treatments in continuous corn or in a crop rotation of corn, sugarbeet, and spring wheat with all three crops resistant to glyphosate. After 6 yr, plant densities of common lambsquarters, redroot pigweed, hairy nightshade, and common purslane increased in the crop-rotation treatment compared with continuous corn. There were four weed control subplot treatments consisting of two in-crop applications of glyphosate at 0.4 or 0.8 kg ae/ha each spring, alternating two applications of glyphosate at 0.8 kg/ha one year with a nonglyphosate treatment the next year, or a nonglyphosate treatment each year. The composition of the weed population averaged across all four treatments shifted from kochia and wild proso millet to predominately common lambsquarters. After 3 yr of using glyphosate at 0.4 kg/ha twice each year, common lambsquarters density increased compared with that in the 0.8 kg/ha rate of glyphosate or alternating glyphosate treatments. By the sixth year, the density of common lambsquarters in the glyphosate at 0.4 kg/ha treatment had increased to the extent that corn grain yield was reduced 43% compared with corn grain yield in the 0.8 kg/ha glyphosate treatment. Using glyphosate at either rate for 6 yr decreased the densities of kochia, wild proso millet, and longspine sandbur, did not alter densities of redroot pigweed and green foxtail, and increased the density of hairy nightshade. In the low-rate treatment of glyphosate, the number of common lambsquarters seeds in the seed bank were 134 seeds/kg soil in 1998, declined to 15 seeds/kg by 2002, but began to increase in 2003 as the densities of plants not controlled by glyphosate increased.

Background:This study examined the prevalence of irritability in patients with bipolar I disorder during an episode of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) major depression who do not meet criteria for a mixed episode.

Method:A chart review of 111 patients with bipolar I disorder treated at the Massachusetts General Hospital Bipolar Clinic between 1998 and 2000 identified 34 patients who met criteria for a DSM-IV major depressive episode in the absence of (1) mood elevation and/or (2) irritability associated with any additional above threshold DSM-IV symptoms of mania. Data gathered from the charts utilized prospective ratings made routinely at each clinic visit using the Clinical Monitoring Form (CMF), a structured assessment instrument which includes modified versions of the mood modules of the Structured Clinical Interview for DSM-IV. Data from these 34 patients were reviewed to determine the presence of irritability.

Results:The frequency of abnormal irritability in these 34 patients followed a bimodal distribution: 26% of the patients showed abnormal irritability ≥75% of the time, compared with 68% of the patients with abnormal irritabihty ≤30% of the time. Of the high-irritability patients, psychomotor agitation was rated as definitely present to a significant degree in 44%. Talkativeness and distractibility were rated present but subthreshold in one patient each. All other symptoms of DSM-IV mania were absent.

Conclusion:Approximately 25% of patients with bipolar I disorder who meet criteria for a DSM-IV major depressive episode also experienced substantial irritability in the absence of associated symptoms of mania. Our results suggest that abnormal irritability is not limited to mania or mixed states.