Rhino-orbito-cerebral mucormycosis: patient characteristics in pre-COVID-19 and COVID-19 period.

BACKGROUND: Rhino-orbito-cerebral-mucormycosis (ROCM), a rare and potentially fatal disease was seen in increasing numbers during the COVID-19 pandemic. This study describes and compares the patient characteristics and outcomes in COVID-19 associated mucormycosis (CAM) and non-COVID-19 mucormycosis (non-CAM). METHODOLOGY: CAM patients (24 cases) were recruited from the COVID-19 period and non-CAM (24 controls) from the pre-COVID-19 period. Clinical data of the CAM group was collected retrospectively with 3 month outcomes prospectively. The non-CAM group data was collected retrospectively. Patient characteristics were compared and risk factors for mortality in ROCM were assessed. RESULTS: Orbital symptoms [altered vision, restricted eye movements, ptosis] and intracranial involvement were higher in CAM patients on presentation. Similarly, the radiological involvement of orbit (orbital apex, superior orbital fissure) and intracranial cavity (intracranial thrombosis, cavernous sinus) was also higher in CAM patients. Newly detected diabetes was found only in CAM patients (29.2%). Although univariate analysis suggested an increased mortality risk in ROCM patients with orbital involvement, the multivariate analysis showed no increased risk with any of the parameters assessed, including COVID-19 positivity. CONCLUSIONS: Compared to the non-CAM, the disease presentation was severe in CAM with higher frequency of orbital and intracranial involvement. However, with early detection and treatment, the short term survival was comparable in both groups.

Revised workflow practices in the management of acute invasive fungal sinusitis during the coronavirus disease 2019 pandemic.

OBJECTIVE: To document changes in evaluation protocols for acute invasive fungal sinusitis during the coronavirus disease 2019 pandemic, and to analyse concordance between clinical and histopathological diagnoses based on new practice guidelines. METHODS: Protocols for the evaluation of patients with suspected acute invasive fungal sinusitis both prior and during the coronavirus disease 2019 period are described. A retrospective analysis of patients presenting with suspected acute invasive fungal sinusitis from 1 May to 30 June 2021 was conducted, with assessment of the concordance between clinical and final diagnoses. RESULTS: Among 171 patients with high clinical suspicion, 160 (93.6 per cent) had a final histopathological diagnosis of invasive fungal sinusitis, concordant with the clinical diagnosis, with sensitivity of 100 per cent, positive predictive value of 93.6 per cent and negative predictive value of 100 per cent. CONCLUSION: The study highlights a valuable screening tool with good accuracy, involving emphasis on 'red flag' signs in high-risk populations. This could be valuable in situations demanding the avoidance of aerosol-generating procedures and in resource-limited settings facilitating early referral to higher level care centres.

The clinical outcomes of medical therapies in chronic rhinosinusitis are independent of microbiomic outcomes: a double-blinded, randomised placebo-controlled trial.

BACKGROUND: Oral and topical corticosteroids, and antibiotics form the mainstay medical treatment of chronic rhinosinusitis (CRS). Clinical outcomes vary depending on the chosen therapy, resident microbiome and disease phenotype. We conducted a double- blinded, placebo-controlled Randomised Controlled Trial (RCT) to investigate effects of medical therapy on clinical outcomes and associated microbiome shifts. METHODOLOGY: Fifty eligible patients (CRS with and without polyps) were treated for 3 weeks after randomisation into 3 arms: na- mely oral prednisolone, topical budesonide irrigations and oral doxycycline; each with appropriate placebo. Clinical scoring and microbiome swabs were performed on enrolment, at treatment completion and 3-weeks post treatment completion. Microbiome analysis was performed using the llumina-MiSeq next generation sequencing platform and QIME-2 pipeline. RESULTS: Significant improvement in clinical scores was observed in prednisolone and budesonide arms at treatment completion but not with antibiotic. Sub-group analysis showed more pronounced effects in patients with polyposis. Corynebacterium and Staphylococcus species predominated, with variable bacterial relative abundance among different treatments at all time-points. The only significant microbiome finding was an increase in bacterial diversity in topical budesonide group immediately after treatment, which returned to baseline 3-weeks post treatment. CONCLUSION: Clinical improvement was significant with oral and topical steroid but not empirical antibiotic. Although there were some associated microbiome changes with the various treatments, we could not ascertain the consistency of these and whether they do have a clinical significance at all.

Mediterranean-Dash Intervention for Neurodegenerative Delay (MIND) Diet Slows Cognitive Decline After Stroke.

OBJECTIVE: This study sought to determine if the MIND diet (a hybrid of the Mediterranean and Dash diets, with modifications based on the science of nutrition and the brain), is effective in preventing cognitive decline after stroke. DESIGN: We analyzed 106 participants of a community cohort study who had completed a diet assessment and two or more annual cognitive assessments and who also had a clinical history of stroke. Cognition in five cognitive domains was assessed using structured clinical evaluations that included a battery of 19 cognitive tests. MIND diet scores were computed using a valid food frequency questionnaire (FFQ). Dietary components of the MIND diet included whole grains, leafy greens and other vegetables, berries, beans, nuts, lean meats, fish, poultry, and olive oil and reduced consumption of cheese, butter, fried foods, and sweets. MIND diet scores were modeled in tertiles. The influence of baseline MIND score on change in a global cognitive function measure and in the five cognitive domains was assessed using linear mixed models adjusted for age and other potential confounders. RESULTS: With adjustment for age, sex, education, APOE-ε4, caloric intake, smoking, and participation in cognitive and physical activities, the top vs lowest tertiles of MIND diet scores had a slower rate of global cognitive decline (ß = .08; CI = 0.0074, 0.156) over an average of 5.9 years of follow-up. CONCLUSIONS: High adherence to the MIND diet was associated with a slower rate of cognitive decline after stroke.

Decoding the 'embryonic' nature of embryonal rhabdomyosarcoma.

Embryonal rhabdomyosarcoma is one of the major defined histologic variants of rhabdomyosarcoma that is mainly reported in children. The histologic appearance of this neoplastic entity recapitulates normal myogenesis. The tumor cells variably exhibit the different cellular phases of myogenesis ranging from undifferentiated mesenchymal cells to elongated myoblasts, multinucleated myotubes and differentiated muscle fibers. The carefully orchestrated embryonic signaling pathways that are involved in myogenesis, conceivably also result in the genesis of rhabdomyosarcoma; albeit as a corollary to an imbalance. We have attempted to review the pathogenesis of embryonal rhabdomyosarcoma in an endeavor to understand better, how closely it is linked to normal myogenesis in terms of its molecular dynamics and histologic presentation.

Nasal in-situ gels for delivery of rasagiline mesylate: improvement in bioavailability and brain localization.

Intranasal thermosensitive gel for rasagiline mesylate (RM) was developed for effective treatment of Parkinson's disease. Intranasal gels were prepared by combination of poloxamer 407 and poloxamer 188 (1:1) with mucoadhesive polymers (carbopol 934 P and chitosan). The formulations were evaluated for sol-gel transition temperature, in-vitro drug release and in-vivo mucociliary transit time. Further, optimal intranasal gel formulations were tested for in-vivo pharmacokinetic behavior, nasal toxicity studies and brain uptake studies. It was found that optimal formulations had acceptable gelation temperature (28-33 °C) and adequate in-vitro drug release profile. Pharmacokinetic study in rabbits showed significant (p < 0.05) improvement in bioavailability (four- to six-folds) of the drug from intranasal gels than oral solution. Chronic exposure studies in Wistar rats showed that these intranasal gels were non-irritant and non-toxic to rat nasal mucosa. Estimation of RM in rat brain tissue showed significant (p < 0.01) improvement in uptake of RM form intranasal gel formulations than nasal solution.

LC method for determination of rasagiline mesylate in different plasma matrices and its application to oral pharmacokinetic study in rabbits.

A simple, rapid and sensitive reverse-phase liquid chromatographic method is developed and validated for estimation of rasagiline mesylate in different plasma matrices (rat, rabbit and human plasma). The method employs an isocratic elution technique with a Kromasil C18 column and has an optimized mobile phase composition of 10 mM ammonium acetate buffer-acetonitrile (40:60 v/v). The plasma samples displayed linear detector responses in the concentration range of 0.5-20 µg/mL in all plasma matrices when monitored at 265 nm using an ultraviolet detector. Because the simple protein precipitation method yields over 95% recovery of rasagiline mesylate from all plasma matrices, no internal standard was used in this method. A detailed validation study of the method proves the accuracy, precision and selectivity (in estimating rasagiline mesylate) in all plasma matrices. The drug is also stable under various processing and storage conditions in all plasma matrices, as evident from the study. The present method was applied to determine the drug-protein binding ratio in all the plasma matrices. The use of this method in determining pharmacokinetic parameters of rasagiline mesylate by non-compartmental analysis after oral dosing in rabbits is also discussed.

Cortical expression of prolactin (PRL), growth hormone (GH) and adrenocorticotrophic hormone (ACTH) is not increased in experimental traumatic brain injury.

BACKGROUND: Cerebral cortical expression of the pituitary hormones prolactin (PRL) and growth hormone (GH) have reported in ischemic damage. Both hormones may be involved in vascular tone regulation and angiogenesis, and growth hormone is thought to be neuroprotective while prolactin stimulates astrogliosis. METHODS: We examined expression of prolactin, growth hormone and adrenocorticotrophic hormone (ACTH) using tissue microarray technology in the controlled cortical impact model of traumatic brain injury (TBI). FINDINGS: No increased expression of these hormones was seen. CONCLUSIONS: Unlike ischemia, traumatic brain injury does not result in up-regulation of the pituitary hormones PRL and GH in cerebral cortex.

Circadian coupling between pancreatic secretion and intestinal motility in humans.

Human interdigestive intestinal motility follows a circadian rhythm with reduced nocturnal activity, but circadian pancreatic exocrine secretion is unknown. To determine whether circadian changes in interdigestive pancreatic secretion occur and are associated with motor events, pancreatic enzyme outputs, proximal jejunal motility, and plasma pancreatic polypeptide concentrations were measured during consecutive daytime and nighttime periods (12 h each) in seven healthy volunteers using orojejunal multilumen intubation. Studies were randomly started in the morning or evening. Nocturnally, motility decreased (motor quiescence: 67 +/- 22 vs. 146 +/- 37 min; motility index: 3.59 +/- 0.33 vs. 2.78 +/- 0.40 mmHg/min; both P < 0.05) but amylase output increased (273 +/- 78 vs. 384 +/- 100 U/min; P < 0.05) and protease output remained unchanged (P > 0.05); consequently, enzyme/motility ratio increased. Amylase outputs were always lowest during phase I. Motor but not pancreatic circadian activities were associated with sleep. Pancreatic polypeptide plasma concentrations were unchanged. Consequently, intestinal motor and pancreatic exocrine functions may have different circadian rhythms, i.e., decreased motor and stable secretory activity during the night. However, the association between individual phases of interdigestive motor and secretory activity is preserved. The nocturnal increase in enzyme/motility ratio is probably not caused by increased cholinergic tone.

Attitudes towards handicaps in South African and Indian university students.

327 first-year students in South Africa showed a significantly more favourable attitude towards handicaps than 205 first-year Indian students.

Concepts and treatment for diabetes among traditional and faith healers in the northern province, South Africa.

The purpose of the study was to assess the concepts and treatment modalities for diabetes among traditional and faith healers in the Northern Province in South Africa. The sample consisted of 50 traditional healers (13 females and 37 males) and 50 faith healers (12 females and 38 males). They were interviewed on local terminology, clinical manifestations, causes, curability, and treatment for diabetes, help-seeking behaviour of diabetes patients, and the healers' sources of information about diabetes. Results indicate that all healers were familiar with "diabetes", however, not all of them had seen patients suffering from diabetes. The perceived causes of diabetes by both traditional and faith healers could be divided into (1) diet (especially too much of sugar), (2) heredity, (3) supernatural, and (4) psychological causes. Most traditional healers (92%) and faith healers (90%) indicated that diabetes is curable. Treatments used by the healers in this study included the use of prayer, diet, and herbs. The authors conclude that the concepts and treatment modalities for diabetes among traditional and faith healers should be taken note of by health workers while developing health education programmes in the Province.

Substance use among urban and rural secondary school pupils in South Africa.

This study investigated the prevalence and frequency of substance use among a sample of 209 urban and 191 rural school pupils in South Africa. The three most predominantly used substances were alcohol, tobacco, and cannabis. Urban and rural differences in substances used were found.

Brain nitric oxide changes after controlled cortical impact injury in rats.

Nitric oxide (NO) and the NO end products, nitrate and nitrite, were measured at the impact site after a 5-m/s, 3-mm deformation controlled cortical impact injury in rats. Immediately after the impact injury and the NO and microdialysis probes could be replaced, there was an increase from baseline in NO concentration of 83 +/- 16 (SE) nM, compared with 0.5 +/- 4 nM in the sham injured animals (P < 0.001). This marked increase in NO occurred at the time of the initial rise in blood pressure (BP) and intracranial pressure (ICP) in response to the injury. After the initial increase in BP and ICP, the BP decreased and stabilized at a value which was approximately 20 mmHg below the preinjury values, and ICP plateaued at an average value of 20 mmHg, compared with 8 mmHg in the sham-injured animals. This provided an average cerebral perfusion pressure of 40-50 mmHg, compared with 65-75 mmHg for the sham-injured animals. These values were relatively constant for the remainder of the 3-h monitoring period. The NO values also stabilized during this time period. By 1 h after the impact injury the NO concentration measured directly using the NO electrode had decreased from baseline values by an average value of 25 +/- 6 nM. NO concentration remained significantly lower than baseline values throughout the remainder of the 3-h monitoring period. The concentration of nitrate/nitrite in the dialysate fluid also decreased by an average value of 341 +/- 283 nM 20-40 min after the injury. Dialysate nitrite/nitrate concentrations remained less than the preinjury baseline values throughout the remainder of the 3-h monitoring period. Preinjury treatment with L-nitro-arginine methyl ester (L-NAME) blunted the injury-induced increase in NO and resulted in more severe immediate intracranial hypertension and more severe systemic hypotension at one hour after injury. Mortality was also 67% with L-NAME pretreatment, compared with 1% in untreated animals.

Cross-cultural attitudes towards suicide among South African secondary school pupils.

OBJECTIVE: To investigate the attitudes towards suicide among Grade II secondary school pupils among three cultural groups in South Africa. DESIGN: Cross sectional study. SETTING: Grade II Secondary school pupils chosen at random from three urban schools in Pietersburg. PARTICIPANTS: The sample included 366 pupils, 150 (41%) males and 216 (59%) females, the mean age was 19.3 years (SD = 2.6), with a range from 17 to 24 years. The three cultural groups were 142 blacks, 112 whites and 112 Asians. MAIN OUTCOME MEASURES: Socioeconomic and family background (14 items), suicide data (4 items), and a 30-item Multi-Attitude Suicide Tendency Scale for Adolescents (MAST-12). RESULTS: Suicide ideation and plans to commit suicide are the highest among Asians, closely followed by Whites and lowest among Black pupils. The frequency of attempted suicide was lower among Blacks (11.3%) than that among Asians (13.5%) and Whites (13%). Analysis of variance indicated a significantly higher score among suicide attempters on attraction to death and repulsion by life and a significantly lower score on attraction to life and repulsion by death. Furthermore, this study found a significant correlation between total MAST, suicide ideation, suicide intent, history of completed suicide in family or friend, parents divorced, family size and suicide attempt. CONCLUSION: This study found differential effects across diverse ethnocultural adolescent groups for suicidal ideation, plants and attempts. This gives indications on how suicide prevention programmes can be constructed in culture-congenial ways.

Knowledge, self-efficacy and behavioural intent towards AIDS prevention behaviours among culturally diverse secondary school pupils in South Africa.

OBJECTIVE: To investigate knowledge, self-efficacy, and behavioural intent towards AIDS prevention behaviours among culturally diverse secondary school pupils in South Africa. DESIGN: Randomised study. SETTING: Three urban secondary schools in Pietersburg, South Africa. PARTICIPANTS: Three hundred and sixty six Grade 11 secondary school pupils, comprising 150 (41%) males, and 216 (59%) females, aged 17 to 24 years (mean age 19.3 years, SD=2.6). The three cultural groups were 142 Blacks, 112 Whites and 112 Asians. MAIN OUTCOME MEASURES: The questionnaire included items on socio-economic and family background, knowledge about HIV, perceived self-efficacy and behavioural intent regarding AIDS preventive behaviours. RESULTS: Overall, the participants showed an adequate level of AIDS knowledge. However, there was considerable inaccuracy regarding AIDS transmission myths or how AIDS cannot be transmitted. The different cultural groups generally felt most self-efficacious regarding how to protect themselves from becoming infected (75-90%) and least self-efficacious on knowing where to go for information on AIDS (72-74%). Generally, participants reported a high behavioural intent. The Whites stand second in knowledge and more or less second in self-efficacy and behaviour intent. The Blacks stand third in knowledge and more or less second in self-efficacy and behaviour intent. CONCLUSION: Culturally diverse knowledge, self-efficacy and behavioural intent towards AIDS prevention was found among White, Black and Asian pupils, which should inform a culturally sensitive and appropriate AIDS health promotion programme in South Africa.

Minor psychiatric morbidity in South African secondary school pupils.

This study investigated minor psychiatric morbidity ("neurotic": anxiety and depression symptoms) in rural (Black) South African secondary school pupils. The sample included 622 Grade 11 pupils (254 boys and 368 girls) in the age range of 17 to 24 years with a mean age of 19.3 yr. The inventories used were a questionnaire on the socioeconomic and family background, a Cultural Orientation Scale, a Student Stress Scale, a General Self-efficacy Scale, a Perceived Stress Scale, and the Self-reporting Questionnaire-20. The findings are that 12.6% of the pupils had a possible clinically significant psychological disorder. Contributing factors identified were interpersonal, study, finance, illness, perceived stress, low self-efficacy, and low religious orientation.

Cerebral hemodynamic effects of phenylephrine and L-arginine after cortical impact injury.

OBJECTIVE: To determine the effects of a pressor agent (phenylephrine and L-arginine) on the abnormal cerebral hemodynamics and on neurologic outcome after a severe cortical impact injury in rats. DESIGN: Prospective, randomized study. SETTING: University laboratory. SUBJECTS: Male Long-Evans rats, weighing 300 to 400 g, fasted overnight. INTERVENTIONS: The animals were anesthetized with isoflurane, and a severe cortical impact injury (velocity, 5 m/sec; deformation, 3 mm) was produced in the right parietal cortex. Five minutes after impact injury, one of the following three treatments were infused: 1 mL saline intravenously for 10 mins, 300 mg/kg L-arginine in 1 mL saline intravenously for 10 mins, or 0.3 microg/kg/min phenylephrine intravenously for 3 hrs. Mean arterial pressure, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and laser Doppler flow (LDF) at the impact site and in the contralateral parietal cortex were monitored for 3 hrs after the impact injury. Histologic examination of the brain was performed at 2 wks after injury in a separate group of L-arginine- and saline-treated animals. MEASUREMENTS AND MAIN RESULTS: The immediate response to the impact injury was an increase in ICP, and a decrease in mean arterial pressure, CPP, and LDF. In the saline-treated animals, LDF decreased to <25% of the baseline values at the impact site and stayed at that level for the entire 3-hr monitoring period. On the contralateral side, LDF decreased initially and recovered gradually to approximately 50% of the preimpact baseline value. Infusion of both phenylephrine and L-arginine increased LDF back to near-baseline levels. However, phenylephrine increased ICP significantly, whereas ICP with L-arginine did not change. L-arginine treatment reduced the contusion volume from a median value of 5.28 mm3 to 0.63 mm3. CONCLUSIONS: Phenylephrine increased cerebral blood flow (CBF) by increasing CPP. L-arginine, however, increased CBF without changing CPP. The improvement in CBF was accompanied by a decrease in neurologic injury. Although the pressor agents are used currently to increase CBF after traumatic brain injury, other strategies may also increase CBF without the potential adverse effects of induced hypertension.

Endothelial-mediated dilations following severe controlled cortical impact injury in the rat middle cerebral artery.

The mechanisms associated with dysfunction of the cerebral vasculature following head trauma have not yet been fully elucidated. In an attempt to shed more light on the matter, we investigated the endothelial-mediated dilations in the rat middle cerebral artery (MCA) following severe traumatic brain injury (TBI). Rats were subjected to severe controlled cortical impact injury (CCI; 5 m/s, 130 ms duration, 3 mm deformation) over the right parietal cortex. At 24 h postinjury, ipsilateral segments of MCA and corresponding contralateral segments were isolated, mounted in a vessel chamber, and pressurized. The responses to 2 methylthio-ATP (2MeSATP), a selective agonist for the P2Y1 purinoceptors, N(omega)-nitro-L-arginine (L-NAME), an NO synthase inhibitor, and S-nitroso-N-acetylpenicillamine (SNAP), an exogenous NO donor, were determined. 2MeSATP elicited concentration dependent dilations in all MCAs studied. Ipsilateral MCAs harvested following TBI or sham-TBI, showed similar maximum dilations to 2MeSATP [70 +/- 4% (n = 17) and 72 +/- 6% (n = 13), respectively]. However, TBI reduced the concentration of 2MeSATP necessary to elicit one-half of the maximum dilation (EC50) from 15 to 9 nM (p < 0.05). Inhibition of NO synthase with 10(-5) M L-NAME abolished the dilation to 2MeSATP in both TBI and sham-TBI MCAs. The constriction to L-NAME was significantly reduced in TBI MCAs compared to sham vessels. Dilations to SNAP, an NO donor, were not altered by TBI indicating that the mechanisms of dilation involving NO in the vascular smooth muscle were not affected. Unlike other pathological conditions which often diminish endothelial-mediated responses, severe TBI enhanced the sensitivity to 2MeSATP without altering the maximum response.

University students' adjustment problems.

Considerable information is available on the adjustment problems of first-year university students in developed countries, but comparatively little is known about such problems in Asia and Africa. This study of a representative sample of 1257 first-year students conducted at the University of the North showed that 33 to 85% of the first-year students experienced various adjustment problems.