Sleep and cognition in South African patients with non-functioning pituitary adenomas.

Strong lines of evidence in the neuroscience literature indicate that (a) healthy sleep facilitates cognitive processing, and (b) sleep disruption is associated with cognitive dysfunction. Despite the fact that patients with pituitary disease often display both disrupted sleep and cognitive dysfunction, few previous studies investigate whether these clinical characteristics in these patients might be related. Hence, we explored whether sleep disruption in patients with pituitary disease mediates their cognitive dysfunction. We recruited 18 patients with non-functioning pituitary adenomas (NFPA) and 19 sociodemographically matched healthy controls. They completed the Global Sleep Assessment Questionnaire (thus providing self-report data regarding sleep disruption) and were administered the Brief Test of Adult Cognition by Telephone, which assesses cognitive functioning in the domains of processing speed, working memory, episodic memory, inhibition, and reasoning. We found no significant differences in cognition between patients and controls. Furthermore, spectra of sleep disturbance did not differ significantly between patients and controls. Our data suggest that NFPA patients' cognition and sleep quality is relatively intact, and that sleep disruption does not mediate cognitive dysfunction. Larger studies should characterize sleep and cognition in patients with NFPA (and other pituitary diseases) to confirm whether disruption of the former mediates impairment in the latter.

Microalgae: potential novel protein for sustainable human nutrition.

To support a global population of ~10 billion people in 2050, dietary protein demand is forecast to increase 32-78% compared to 2017, requiring significantly higher planetary resources. Microalgae are an attractive sustainable protein source compared with current plant and animal sources. Benefits include mass scalability, low CO2 emissions, and significantly reduced land and freshwater use per unit protein. Microalgae are already used as food products and numerous species exhibit high total protein contents and well-balanced essential amino acid (EAA) compositions for human dietary requirements. Microalgae proteins are also bioavailable for human digestion, and downstream processing steps are likely to further enhance protein digestibility. Species, cultivation, and process/product optimisation are actively being developed to enhance their nutritional, social, and environmental benefits.

Management of Type 2 Diabetes Mellitus and Kidney Failure in People with HIV-Infection in Africa: Current Status and a Call to Action.

There is an increasing global burden of diabetes mellitus (DM) and chronic kidney disease (CKD), coupled with a high burden of people with HIV (PWH). Due to an increased lifespan on ART, PWH are now at risk of developing non-communicable diseases, including DM. Africa has the greatest burden of HIV infection and will experience the greatest increase in prevalence of DM over the next two decades. In addition, there is a rising number of people with CKD and progression to kidney failure. Therefore, there is an urgent need for the early identification and management of all 3 diseases to prevent disease progression and complications. This is particularly important in Africa for people with CKD where there is restricted or no access to dialysis and/or transplantation. This review focuses on the epidemiology and pathophysiology of the interaction between HIV infection and DM and the impact that these diseases have on the development and progression of CKD. Finally, it also aims to review the data on the management, which stems from the growing burden of all three diseases.

Outcome of COVID-19 infections in patients with adrenal insufficiency and excess.

Background: Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce. Methods: A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing's syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021. Results: Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison's disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission. Conclusion: This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules.

Characteristics and Challenges of Primary Adrenal Insufficiency in Africa: A Review of the Literature.

Backgrounds: Africa comprises 54 countries with varying degrees of economic development. As with other healthcare systems, rare diseases such as adrenal insufficiency are neglected and poorly documented. Objectives: We wished to explore primary adrenal insufficiency (PAI) in Africa, its prevalence, aetiology, genetics, presentation, diagnosis, and treatment and to determine the unmet needs in clinical care, education, and research. Materials and Methods: A narrative nonsystematic review of the literature was undertaken. We searched two online databases (PubMed and Google scholar) using the search terms "Addison's disease/PAI, primary adrenal insufficiency coupled with "Africa," "country names," and "genetic disorders." A total of 184 PAI records were reviewed. The exclusion of abstracts, conference proceedings, single case reports, and duplicate studies covering the same subject matter yielded 124 articles, of which 97 informed the final manuscript. Results: A wide range of aetiology of PAI was encountered, but their true prevalence is unknown. Aetiology varied with region and age of presentation as reflected by predominantly TB, HIV, and infective causes occurring in sub-Saharan Africa and more congenital forms described in North Africa associated with consanguinity. In Africa, the diagnostic criteria for PAI do not universally accord with conventional criteria, and there is a heavy reliance on clinical suspicion and biochemistry, including random cortisol of <400 nmol/L, rather than the tetracosactide test where stimulated cortisol <500-550 nmol/L confirms the diagnosis. Conclusions: A high index of suspicion is warranted to diagnose PAI in resource-limited settings, especially where tetracosactide tests are not universally available.

Reference intervals for biochemical analytes in transgender individuals on hormone therapy.

BACKGROUND: Hormone therapy in transgender individuals may impact processes that lead to changes in biochemical analytes, and therefore reference intervals. Currently, few reference interval studies are available for the transgender population. We determined biochemical reference intervals for transgender individuals receiving hormone therapy. METHODS: Our retrospective, laboratory-based, observational study included healthy transgender males (N = 24) and transgender females (N = 84) on hormone therapy. Various biochemical reference intervals were established for each cohort and compared to their cisgender counterparts. RESULTS: We detected significant differences in reference intervals for sodium, 139-142 mmol/L vs. 136-145 mmol/L when comparing transgender males (TM) with cisgender males (CM). The following significant changes in upper reference limits (URL) for TM versus CM were detected, ALP (URL: 96 U/L vs. 128 U/L), GGT (URL: 27 U/L vs. 67 U/L) and testosterone (URL: 46.7 nmol/L vs. 29.0 nmol/L), respectively. Moreover, when comparing transgender female (TF) to cisgender female (CF), significant differences in creatinine (URL: 117 µmol/L vs. 90 µmol/L), albumin (lower reference limit: 41 g/L, vs. 35 g/L), AST (URL: 50 U/L vs. 35 U/L), ALP (URL: 118 U/L vs. 98 U/L) and oestradiol (URL: 934 pmol/L vs. 213 pmol/L) were noted, respectively. Significantly higher LDL-C was observed for TM on hormone treatment, compared to baseline (2.9 mmol/L vs. 2.2 mmol/L, p <0.01). CONCLUSIONS: Biochemical results for TM and TF receiving hormone therapy can be evaluated against our transgender-specific reference intervals for some analytes, while others can be compared to their identified gender reference intervals.

Microalgal nanocellulose - opportunities for a circular bioeconomy.

Over 3 billion years, photosynthetic algae have evolved complex uses for cellulose, the most abundant polymer worldwide. A major cell-wall component of lignocellulosic plants, seaweeds, microalgae, and bacteria, cellulose can be processed to nanocellulose, a promising nanomaterial with novel properties. The structural diversity of macro- and microalgal nanocelluloses opens opportunities to couple low-impact biomass production with novel, green-chemistry processing to yield valuable, sustainable nanomaterials for a multitude of applications ranging from novel wound dressings to organic solar cells. We review the origins of algal cellulose and the applications and uses of nanocellulose, and highlight the potential for microalgae as a nanocellulose source. Given the limited state of current knowledge, we identify research challenges and strategies to help to realise this potential.

Risk factors for COVID-19 hospitalisation and death in people living with diabetes: A virtual cohort study from the Western Cape Province, South Africa.

BACKGROUND: COVID-19 outcomes and risk factors, including comorbidities and medication regimens, in people living with diabetes (PLWD) are poorly defined for low- and middle-income countries. METHODS: The Provincial Health Data Centre (Western Cape, South Africa) is a health information exchange collating patient-level routine health data for approximately 4 million public sector health care seekers. Data from COVID-19 patients diagnosed between March and July 2020, including PLWD, were analysed to describe risk factors, including dispensed diabetes medications and comorbidities, and their association with COVID-19 outcomes in this population. FINDINGS: There were 64,476 COVID-19 patients diagnosed. Of 9305 PLWD, 44.9% were hospitalised, 4.0% admitted to ICU, 0.6% received ventilation and 15.4% died. In contrast, proportions of COVID-19 patients without diabetes were: 12.2% hospitalised, 1.0% admitted, 0.1% ventilated and 4.6% died. PLWD were significantly more likely to be admitted (OR:3.73, 95 %CI: 3.53, 3.94) and to die (OR:3.01, 95 %CI: 2.76,3.28). Significant hospitalised risk factors included HIV infection, chronic kidney disease, current TB, male sex and increasing age. Significant risk factors for mortality were CKD, male sex, HIV infection, previous TB and increasing age. Pre-infection use of insulin was associated with a significant increased risk for hospitalisation (OR:1·39, 95 %CI:1·24,1·57) and mortality (OR1·49, 95 %CI:1·27; 1·74) and metformin was associated with a reduced risk for hospitalisation (OR:0·62,95 %CI:0·55, 0·71) and mortality (OR 0·77, 95 %CI:0·64; 0·92). INTERPRETATION: Using routine health data from this large virtual cohort, we have described the association of infectious and noncommunicable comorbidities as well as pre-infection diabetes medications with COVID-19 outcomes in PLWD in the Western Cape, South Africa. FUNDING: This research was funded in part, by the Wellcome Trust 203135/Z/16/Z, through support of NT. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The Wellcome Centre for Infectious Diseases Research in Africa is supported by core funding from the Wellcome Trust [203135/Z/16/Z]. NT receives funding from the CIDRI-Africa Wellcome Trust grant (203135/Z/16/Z), and NT and TT receive funding from the NIH H3ABioNET award (U24HG006941). NT receives funding from the UKRI/MRC (MC_PC_MR/T037733/1).

Tiered healthcare in South Africa exposes deficiencies in management and more patients with infectious etiology of primary adrenal insufficiency.

OBJECTIVE: We wished to determine the prevalence, etiology, presentation, and available management strategies for primary adrenal insufficiency (PAI) in South Africa (SA), hypothesizing a prevalence greater than the described 3.1 per million. There is great inequity in healthcare allocation, as two parallel healthcare systems exist, potentially modifying PAI patients' clinical profiles, private being better resourced than public healthcare. METHODS: An online survey of physicians' experience relating to PAI. RESULTS: The physicians were managing 811 patients, equal to a prevalence of 14.2 per million. Likely causes of PAI in public/ academic vs private settings included: AIDS-related [304 (44.8%) vs 5 (3.8%); p<0.001], tuberculosis [288 (42.5%) vs 8 (6.0%); p<0.001], autoimmune disease [50 (7.4%) vs 88 (66.2%); p<0.001], malignancy [27 (4.0%) vs 7 (5.3%); p = 0.500], genetic including adrenoleukodystrophy (ALD) [5 (0.7%) vs 16 (12.0%); p<0.001], respectively. Overall, more patients presented with nausea [101 (74.3%) and vomiting 89 (65.9%), than diarrhoea 76 (58.9%); p = 0.008 and 126 (15.5%) in adrenal crisis. Features suggestive of a crisis were hypoglycaemia [40 (78.4%) vs 42 (48.8%); p = 0.001], shock [36 (67.9%) vs 31(36.9%); p<0.001], and loss of consciousness [25 (52.1%) vs 27 (32.9%); p = 0.031]. Greater unavailability of antibody testing in the public vs. the private sector [32 (66.7%) vs 30 (32.1%); p = 0.001], [serum-ACTH 25 (52.1%) vs 16 (19.5%); p<0.001] and glucocorticoids were [26 (54.2%) vs 33 (40.2%); p = 0.015]. Many patients, 389(66.7%) were not using identification, indicating that they need steroids in an emergency. CONCLUSION: A survey of South African physicians suggests a higher prevalence than previously reported. Patients presented with typical symptoms, and 15.5% presented in adrenal crisis. Significant disparities in the availability of physicians' expertise, diagnostic resources, and management options were noted in the public versus private settings. Greater awareness among health practitioners to timeously diagnose PAI is required to prevent a life-threatening outcome.

Detection and identification of dermatophyte fungi in clinical samples using a commercial multiplex tandem PCR assay.

We evaluated the performance of a commercial multiplex tandem polymerase chain reaction (PCR) for detection of dermatophytes and other fungi in skin and nail specimens by (1) testing a range of fungal and bacterial reference cultures, (2) retrospectively testing a set of skin and nail specimens with known microscopy and culture results, and (3) prospectively testing skin and nail specimens in parallel to microscopy and culture. The AusDiagnostics Dermatophytes and Other Fungi assay accurately detected and identified a range of common dermatophytes to species, species complex or genus level, as well as Candida, Aspergillus and Scopulariopsis spp. It was unable to detect uncommon dermatophytes such as Nannizzia fulva (previously Microsporum fulvum), and Paraphyton cookei (previously Microsporum cookei). PCR identified a dermatophyte in 25.9% of prospective specimens which were culture negative. Sensitivity, specificity, positive predictive value, and negative predictive value were highest where microscopy and PCR results were combined, versus microscopy and culture combined, which highlights the significant contribution of microscopy in the diagnostic pathway. This assay has the potential to reduce the workload and results turnaround time associated with culturing and identification of dermatophytes, although microscopy remains important.

Significant barriers to diagnosis and management of adrenal insufficiency in Africa.

BACKGROUND: The burden and management of primary adrenal insufficiency (PAI) in Africa have not been well documented. We aimed to identify specific disease characteristics, patient demographics, and patterns of clinical management in established PAI in Africa. METHODS: An online survey of physicians' experience relating to PAI. RESULTS: There were 1334 responses received, 589 were complete, and 332 respondents reported managing patients with hypoadrenalism. The described responses were related to a calculated pool of 5787 patients with hypoadrenalism (2746 females, 3041 males), of whom 2302 had PAI. The likely causes of PAI in Sub-Saharan Africa (SSA) vs the Middle East and North Africa (MENA) regions included autoimmune disease (20% vs 60.3%; P < 0.001), tuberculosis (34% vs 4.1%; P < 0.001), AIDS (29.8% vs 1%; P < 0.001), malignancy, and genetic conditions. Sixteen percent of AD patients (376/2302) presented in an adrenal crisis. Medical emergency identification was not used by 1233 (83.6%) SSA vs 330 (40.4%) MENA patients (P < 0.001), respectively. Relative non-availability of diagnostic tests across both regions included adrenal antibodies 63% vs 69.6% (P = 0.328), s-cortisol 49.4 % vs 26.7% (P = 0.004), s-ACTH 55.7% vs 53.3% (P = 0.217), and adrenal CT scans 52.4% vs 31.8% (P = 0.017) in the SSA and MENA region, respectively. Across the entire cohort, the overall hydrocortisone use and extrapolated proportion of synacthen use were 59.4% and 50.7%, respectively. CONCLUSIONS: Through the perception and practice of healthcare professionals, we identified significant challenges in the diagnosis and management of PAI which may herald high mortality. Differences between regions may reflect the allocation of healthcare resources.

Structure of a PSI-LHCI-cyt b6f supercomplex in Chlamydomonas reinhardtii promoting cyclic electron flow under anaerobic conditions.

Photosynthetic linear electron flow (LEF) produces ATP and NADPH, while cyclic electron flow (CEF) exclusively drives photophosphorylation to supply extra ATP. The fine-tuning of linear and cyclic electron transport levels allows photosynthetic organisms to balance light energy absorption with cellular energy requirements under constantly changing light conditions. As LEF and CEF share many electron transfer components, a key question is how the same individual structural units contribute to these two different functional modes. Here, we report the structural identification of a photosystem I (PSI)-light harvesting complex I (LHCI)-cytochrome (cyt) b6f supercomplex isolated from the unicellular alga Chlamydomonas reinhardtii under anaerobic conditions, which induces CEF. This provides strong evidence for the model that enhanced CEF is induced by the formation of CEF supercomplexes, when stromal electron carriers are reduced, to generate additional ATP. The additional identification of PSI-LHCI-LHCII complexes is consistent with recent findings that both CEF enhancement and state transitions are triggered by similar conditions, but can occur independently from each other. Single molecule fluorescence correlation spectroscopy indicates a physical association between cyt b6f and fluorescent chlorophyll containing PSI-LHCI supercomplexes. Single particle analysis identified top-view projections of the corresponding PSI-LHCI-cyt b6f supercomplex. Based on molecular modeling and mass spectrometry analyses, we propose a model in which dissociation of LHCA2 and LHCA9 from PSI supports the formation of this CEF supercomplex. This is supported by the finding that a Δlhca2 knockout mutant has constitutively enhanced CEF.

Effect of prednisolone on inflammatory markers in pericardial tuberculosis: A pilot study.

BACKGROUND: Pericardial disorders are a common cause of heart disease, and the most common cause of pericarditis in developing countries is tuberculous (TB) pericarditis. It has been shown that prednisolone added to standard anti-TB therapy leads to a lower rate of constrictive pericarditis. We conducted a pilot study to evaluate the effect of adjunctive prednisolone treatment on the concentration of inflammatory markers in pericardial tuberculosis, in order to inform immunological mechanisms at the disease site. METHODS: Pericardial fluid, plasma and saliva samples were collected from fourteen patients with pericardial tuberculosis, at multiple time points. Inflammatory markers were measured using multiplex luminex analysis and ELISA. RESULTS: In samples from 14 patients we confirmed a strongly compartmentalized immune response at the disease site and found that prednisolone significantly reduced IL-6 concentrations in plasma by 8 hours of treatment, IL-1beta concentrations in saliva, as well as IL-8 concentrations in both pericardial fluid and saliva by 24 hours. CONCLUSION: Monitoring the early effect of adjunctive immunotherapy in plasma or saliva is a possibility in pericarditis.

SCIMP is a transmembrane non-TIR TLR adaptor that promotes proinflammatory cytokine production from macrophages.

Danger signals activate Toll-like receptors (TLRs), thereby initiating inflammatory responses. Canonical TLR signalling, via Toll/Interleukin-1 receptor domain (TIR)-containing adaptors and proinflammatory transcription factors such as NF-κB, occurs in many cell types; however, additional mechanisms are required for specificity of inflammatory responses in innate immune cells. Here we show that SCIMP, an immune-restricted, transmembrane adaptor protein (TRAP), promotes selective proinflammatory cytokine responses by direct modulation of TLR4. SCIMP is a non-TIR-containing adaptor, binding directly to the TLR4-TIR domain in response to lipopolysaccharide. In macrophages, SCIMP is constitutively associated with the Lyn tyrosine kinase, is required for tyrosine phosphorylation of TLR4, and facilitates TLR-inducible production of the proinflammatory cytokines IL-6 and IL-12p40. Point mutations in SCIMP abrogating TLR4 binding also prevent SCIMP-mediated cytokine production. SCIMP is, therefore, an immune-specific TLR adaptor that shapes host defence and inflammation.

Anti-Retroviral Therapy Increases the Prevalence of Dyslipidemia in South African HIV-Infected Patients.

PURPOSE: Data on the prevalence of dyslipidaemia and associated risk factors in HIV-infected patients from sub-Saharan Africa is sparse. We performed a cross-sectional analysis in a cohort of HIV-infected South African adults. METHODS: We studied HIV-infected patients who were either antiretroviral therapy (ART)-naive or receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based ART. Evaluation included fasting lipograms, oral glucose tolerance tests and clinical anthropometry. Dyslipidemia was defined using the NCEP ATPIII guidelines. RESULTS: The median age of the participants was 34 years (range 19-68 years) and 78% were women. The prevalence of dyslipidemia in 406 ART-naive and 551 participants on ART was 90.0% and 85%, respectively. Low HDL-cholesterol (HDLC) was the most common abnormality [290/406 (71%) ART-naïve and 237/551 (43%) ART- participants]. Participants on ART had higher triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLC) and HDLC than the ART-naïve group. Severe dyslipidaemia, (LDLC> 4.9 mmol/L or TG >5.0 mmol/L) was present in <5% of participants. In multivariate analyses there were complex associations between age, gender, type and duration of ART and body composition and LDLC, HDLC and TG, which differed between ART-naïve and ART-participants. CONCLUSION: Participants on ART had higher TG, TC, LDLC and HDLC than those who were ART-naïve but severe lipid abnormalities requiring evaluation and treatment were uncommon.

Poor quality of life, depressed mood, and memory impairment may be mediated by sleep disruption in patients with Addison's disease.

Standard replacement therapy for Addison's disease (AD) does not restore a normal circadian rhythm. In fact, hydrocortisone replacement in AD patients likely induces disrupted sleep. Given that healthy sleep plays an important role in improving quality of life, optimizing cognition, and ensuring affect regulation, the aim of this study was to investigate whether poor quality of life, mood alterations, and memory complaints reported by AD patients are associated with their disrupted sleep patterns. Sixty patients with AD and 60 matched healthy controls completed a battery of self-report questionnaires assessing perceived physical and mental health (Short-Form 36), mood (Beck Depression Inventory-II), sleep quality (Pittsburgh Sleep Quality Index), and cognition (Cognitive Failures Questionnaire). A latent variable model revealed that although AD had a significant direct effect on quality of life, the indirect effect of sleep was significantly greater. Furthermore, although AD had no direct effect on cognitive functioning, the indirect effect of sleep was significant. The overall model showed a good fit (comparative fit index = 0.91, root mean square of approximation = 0.09, and standardized root mean square residual = 0.05). Our findings suggest that disrupted sleep, and not the disease per se, may induce poor quality of life, memory impairment, and affect dysregulation in patients with AD. We think that improving sleep architecture may improve cognitive, affective, and physical functioning.

Solution structure of the RNA-binding cold-shock domain of the Chlamydomonas reinhardtii NAB1 protein and insights into RNA recognition.

Light-harvesting complex (LHC) proteins are among the most abundant proteins on Earth and play critical roles in photosynthesis, both in light capture and in photoprotective mechanisms. The Chlamydomonas reinhardtii nucleic acid-binding protein 1 (NAB1) is a negative regulator of LHC protein translation. Its N-terminal cold-shock domain (CSD) binds to a 13-nt element [CSD consensus sequence (CSDCS)] found in the mRNA of specific LHC proteins associated with Photosystem II (PSII), an interaction which regulates LHC expression and, consequently, PSII-associated antenna size, structure and function. In the present study, we elucidated the solution structure of the NAB1 CSD as determined by heteronuclear NMR. The CSD adopts a characteristic five-stranded anti parallel ß-barrel fold. Upon addition of CSDCS RNA, a large number of NMR chemical shift perturbations were observed, corresponding primarily to surface-exposed residues within the highly conserved ß2- and ß3-strands in the canonical RNA-binding region, but also to residues on ß-strand 5 extending the positive surface patch and the overall RNA-binding site. Additional chemical shift perturbations that accompanied RNA binding involved buried residues, suggesting that transcript recognition is accompanied by conformational change. Our results indicate that NAB1 associates with RNA transcripts through a mechanism involving its CSD that is conserved with mechanisms of sequence-specific nucleic acid recognition employed by ancestrally related bacterial cold-shock proteins (CSPs).

Sulphur responsiveness of the Chlamydomonas reinhardtii LHCBM9 promoter.

MAIN CONCLUSION: A 44-base-pair region in the Chlamydomonas reinhardtii LHCBM9 promoter is essential for sulphur responsiveness. The photosynthetic light-harvesting complex (LHC) proteins play essential roles both in light capture, the first step of photosynthesis, and in photoprotective mechanisms. In contrast to the other LHC proteins and the majority of photosynthesis proteins, the Chlamydomonas reinhardtii photosystem II-associated LHC protein, LHCBM9, was recently reported to be up-regulated under sulphur deprivation conditions, which also induce hydrogen production. Here, we examined the sulphur responsiveness of the LHCBM9 gene at the transcriptional level, through promoter deletion analysis. The LHCBM9 promoter was found to be responsive to sulphur deprivation, with a 44-base-pair region between nucleotide positions -136 and -180 relative to the translation start site identified as essential for this response. Anaerobiosis was found to enhance promoter activity under sulphur deprivation conditions, however, alone was unable to induce promoter activity. The study of LHCBM9 is of biological and biotechnological importance, as its expression is linked to photobiological hydrogen production, theoretically the most efficient process for biofuel production, while the simplicity of using an S-deprivation trigger enables the development of a novel C. reinhardtii-inducible promoter system based on LHCBM9.

Embryological and molecular development of the adrenal glands.

In this mini review, the embryological and functional development of the adrenal glands is presented from a molecular perspective. While acknowledging that this is a highly complex series of events, the processes are described in simple and broad strokes in a single text for the reader who is interested in this field but is not an active researcher. The origin of the adrenal glands is in the mesodermal ridge as early as the fourth week of gestation. Between the eighth and ninth weeks of gestation, the adrenal glands are encapsulated and this results in the presence of a distinct organ. There have been great strides in deciphering the very complicated molecular aspects of adrenal gland development in which multiple transcription factors have been identified, directing the adrenogonadal primordium into the adrenal cortex, kidney, or bipotential gonad. Adrenocorticotrophic hormone is critical for early development of the hypothalamic-pituitary adrenal axis. Several mutations in transcription factors, responsible for normal adrenal gland development have been found to induce the familial syndrome of congenital adrenal hypoplasia or neoplasia.

Poor Penetration of Antibiotics Into Pericardium in Pericardial Tuberculosis.

Pericardial tuberculosis (TB) is associated with high therapy failure and high mortality rates. Antibiotics have to penetrate to site of infection at sufficient non-protein bound concentrations, and then enter bacteria to inhibit intracellular biochemical processes. The antibiotic concentrations achieved in pericardial fluid in TB pericarditis have never been measured before. We recruited two cohorts of patients with TB pericarditis, and left a pigtail catheter in-situ for serial drug concentration measurements over 24 h. Altogether, 704 drug concentrations were comodeled for pharmacokinetic analyses. The drug concentrations achieved in pericardial fluid were compared to the minimum inhibitory concentrations (MICs) of clinical Mycobacterium tuberculosis isolates. The total rifampicin concentration pericardial-to-serum ratios in 16 paired samples were 0.19 ± 0.33. The protein concentrations of the pericardial fluid in TB pericarditis were observed to be as high as in plasma. The non-protein bound rifampicin concentrations in pericardial fluid were 4-fold lower than rifampicin MICs in the pilot study, and the peak concentration was 0.125 versus 0.208 mg/L in the second (p = 0.001). The rifampicin clearance from pericardial fluid was 9.45 L/h versus 7.82 L/h in plasma (p = 0.002). Ethambutol peak concentrations had a pericardial-to-plasma ratio of 0.55 ± 0.22; free ethambutol peak concentrations were 2.30-lower than MICs (p < 0·001). The pericardial fluid pH was 7.34. The median pyrazinamide peak concentrations were 42.93 mg/L versus a median MIC of 800 mg/L at pH 7.34 (p < 0.0001). There was no significant difference between isoniazid pericardial fluid and plasma concentrations, and isoniazid peak concentrations were above MIC. This is the first study to measure anti-TB drug concentrations, pH and protein in the pericardial TB fluid. Pericardial concentrations of the key sterilizing drugs for TB were below MIC, which could contribute to poor outcomes. A new regimen that overcomes these limitations might need to be crafted.