Two new rotenoid glycosides from the rhizomes of Stemona curtisii Hook. f.

Two new rotenoid glycosides named stemonal 11-O-ß-D-glucopyranoside and 6-O-methylstemonal 11-O-ß-D-glucopyranoside together with ten known metabolites were isolated from the rhizomes of Stemona curtisii. The chemical structures of the new compounds were elucidated based on the analysis of their 1D and 2D NMR and HRESIMS, while the sugar unit and absolute configuration were determined by chemical hydrolysis and ECD analysis. Among the tested compounds for anti-α-glucosidase assay, stemonal showed an inhibitory effect (IC50 = 38.67 µM), which is 2.4-fold more potent than acarbose. Cytotoxic evaluation against the lung adenocarcinoma A549 cell line indicated that none of the compounds were strongly active to suppress the cancer cell growth at 100 µM. This work describes the occurrence of rotenoids bearing a sugar moiety, which are reported for the first time in the genus Stemona. The isolated compound's α-glucosidase inhibitory potential provides insight for further investigation of natural rotenoids as anti-diabetic agents.

Characteristics and outcomes of patients hospitalized with COVID-19 at a tertiary hospital in Nigeria.

Background: Data regarding the features and outcomes of hospitalized COVID-19 patients in Africa are increasingly available. Objectives: To describe socio-demographic, clinical and laboratory characteristics and outcomes of COVID-19 patients. Methods: A cross-sectional study of 86 adult patients hospitalized with COVID-19 between March and November 2020. Characteristics were described in survivors and non-survivors. Results: Mean age was 60.9±16.1 years, 53(61.6%) were male. Co-morbidities were found in 77(89.5%) patients. On severity, 6(7%) were mild, 23(26.7%) moderate, 51(59.3%) severe and 6(7%) critical. Oxygen saturation and respiratory rate were 71±22% and 38±11/minute in non-survivors and 90±7% and 31±7/minute in survivors respectively (p<0.001, p<0.001)). Overall mortality was 47.7% with no death among patients with mild disease and deaths in all patients with critical disease. Duration of hospitalization was 2.0(1.0-4.5) days in those who died and 12(7.0-15.0) days in those who survived (p<0.001). Of the 42 patients that received dexamethasone, 11(26.2%) died, while 31(73.8%) survived (p=<0.001). Conclusion: Most of the patients had co-morbidities and there was high mortality in patients with severe and critical COVID-19. Mean oxygen saturation was low and respiratory rate high overall. Factors associated with mortality included: Significantly greater hypoxia and tachypnea, less dexamethasone use and shorter hospitalization.

Clinical profile and outcome of surgical management of intramedullary spinal cord tumours: A single center study in a developing country.

Objective: There is as yet a paucity of data on intramedullary spinal cord tumours (IMSCTs) in sub-Saharan Africa. This study aims to define the clinical profile and outcome of management of IMSCTs in a Nigerian tertiary hospital. Methods: This is a retrospective study of all the patients who had surgery for IMSCTs in our hospital over a 14 year period. Results: There were 20 patients, 9 males, 11 females, in this study. The median age was 33 years (range = 7-78 years). The median duration of symptoms was 12 months (range = 1-120 months). Motor deficit was present in all but one (95%) of our patients. Only 25% of the patients presented in good functional status (McCormick grades I and II). The tumours were confined to the thoracic region in 10 patients (50%), while tumours in the thoracic region extending to the adjoining cervical and lumbar regions were seen in 6 patients (30%). Gross total tumour resection was achieved in 60% of the patients and subtotal resection in the remaining 40%. Astrocytoma and ependymoma were the most common tumours, each occurring in 35% of the cases. Six patients (30.0%) improved, 12 patients (60.0%) remained neurologically the same, while 2 patients (10.0%) deteriorated at the time of last follow up. The mortality rate was 15%. The preoperative functional status was a significant predictor of postoperative outcome (p = 0.03). Conclusion: Astrocytoma and ependymoma were the most common histological tumour types among our patients. Late presentation and poor pre-operative functional status were prominent features of our patients' cohort.

Navigating the learning curve with large and giant tumors: Initial experience with endoscopic endonasal transphenoidal resection of PitNETs.

BACKGROUND: The endoscopic endonasal approach (EEA) has progressively become the preferred choice of surgical intervention for PitNETs. However, the adoption in Sub-Saharan Africa has been low. We report our initial experience with the utility of the EEA in PitNETs particularly in large and giant tumors despite limited resources. METHODS: The study was over a 73-month period at the University College Hospital, Ibadan, Nigeria. Pre and post-operative clinical, imaging and neuro-ophthalmological findings were documented. Perioperative and postoperative outcomes were recorded. We compared the outcomes between the early 23 and later 22 patients. Data were analyzed using descriptive statistics, student's t test, Mann-Whitney U test and Chi square test at α = 0.05. RESULTS: There were 45 patients; 25(55.6%) were males. Mean age was 49.9 ± 13.4 years. Visual symptoms predominated with 12(26%) blind in at least one eye. Median tumor volume was 20.9 cm3 and mean tumor diameter was 4.09 ± 0.89 cm. 31(68.9%) had gross or near total excision. Vision improved in 31(68.9%). There were 2 procedure related mortality from CSF leak/meningitis. The mean of the tumor diameter of the earlier patients was less than that of the latter (3.84 vs 4.40 cm, p = 0.04,). The latter group also had more gross or near total resections (26.8% versus 41.5%) but this was not statistically significant. There was no difference in postoperative complications. CONCLUSIONS: EEA remains a veritable option for PitNETs, including for large and huge tumors, even within resource challenged environments, with acceptable limits of complications.

Post-Inflammatory Hyperpigmentation in Dark Skin: Molecular Mechanism and Skincare Implications.

Human skin is characterized by significant diversity in color and tone, which are determined by the quantity and distribution of melanin pigment in the epidermis. Melanin absorbs and reflects ultraviolet radiation (UVR), preventing the damage to genomic DNA in the epidermis and degradation of collagen in the dermis; therefore, darker skin types are thought to be well protected from the photodamage because of the high melanin content. However, increased content of melanin in combination with the extrinsic stress factors causing inflammation such as excess UVR, allergic reactions, or injury can also frequently lead to cosmetic problems resulting in discoloration and scarring. This review summarizes current knowledge on histopathology and likely molecular signatures of one of the most common problems, post-inflammatory hyperpigmentation (PIH). The mechanisms proposed so far are subsequently discussed in the context of other factors characterizing darker skin types. This includes the common cellular features, organization of upper skin layers, and major biomarkers, with particular emphasis on increased propensities to systemic and localized inflammation. Enhanced or prolonged inflammatory responses can not only affect the process of melanogenesis but also have been implicated in injury-related skin pathologies and aging. Finally, we summarize the major cosmetic treatments for PIH and their known anti-inflammatory targets, which can be beneficial for darker skin tones and combined with broad-spectrum filters against UVR.

Evaluation of Personalized Skincare Through in-silico Gene Interactive Networks and Cellular Responses to UVR and Oxidative Stress.

Purpose: Personalized approaches in dermatology are designed to match the specific requirements based on the individual genetic makeup. One major factor accounting for the differences in skin phenotypes is single nucleotide polymorphism (SNP) within several genes with diverse roles that extend beyond skin tone and pigmentation. Therefore, the cellular sensitivities to the environmental stress and damage linked to extrinsic aging could also underlie the individual characteristics of the skin and dictate the unique skin care requirements. This study aimed to identify the likely biomarkers and molecular signatures expressed in skin cells of different ethnic backgrounds, which could aid further the design of personalized skin products based on specific demands. Methods: Using data mining and in-silico modeling, the association of SNP-affected genes with three major skin types of European, Asian and African origin was analyzed and compared within the structure-function gene interaction networks. Cultured dermal fibroblasts were subsequently subjected to ultraviolet radiation and oxidative stress and analyzed for DNA damage and senescent markers. The protective applications of two cosmetic ingredients, Resveratrol and Quercetin, were validated in both cellular and in-silico models. Results: Each skin type was characterized by the presence of SNPs in the genes controlling facultative and constitutive pigmentation, which could also underlie the major differences in responses to photodamage, such as oxidative stress, inflammation, and barrier homeostasis. Skin-type-specific dermal fibroblasts cultured in-vitro demonstrated distinctive sensitivities to ultraviolet radiation and oxidative stress, which could be modulated further by the bioactive compounds with the predicted capacities to interact with some of the genes in the in-silico models. Conclusion: Evaluation of the SNP-affected gene networks and likely sensitivities of skin cells, defined as low threshold levels to extrinsic stress factors, can provide a valuable tool for the design and formulation of personalized skin products that match more accurately diverse ethnic backgrounds.

Anti-Glycation and Anti-Aging Properties of Resveratrol Derivatives in the in-vitro 3D Models of Human Skin.

Purpose: Human skin undergoes modifications affecting its structural properties and barrier functions involved in protection against age-related damage. Glycation is a non-enzymatic reaction between macromolecules and sugars causing alterations to the elastic fibers and premature aging of the skin. Glycation can be prevented by a range of bioactive molecules; however, at present only a few of them are validated for inclusion in cosmetic products. There is also a demand for reproducible in-vitro assays demonstrating the anti-aging effect of compounds on the skin. This study aimed to define the potential targets for screening and validation of anti-glycation activity of novel cosmetic candidates from natural products and to provide a plausible mechanism for their anti-aging potential based on 3D skin models. Methods: Dermal fibroblasts and 3D skin models were treated with glycation agent and topical applications of Resveratrol derivatives. The samples were analyzed for advanced glycation end products (AGEs) alongside an organization of elastic fibers and expression of proliferative, senescence, and oxidative stress markers by autofluorescence, immunocytochemistry and quantitative assays. Results: Accumulation of AGEs in the 3D skin model is associated with reduced stratification of the epidermis and re-organization of the collagen in the upper, cell-dense layer of the dermis. Treatment of dermal fibroblasts with Resveratrol, OxyResveratrol, Piceatannol, and Triacetyl Resveratrol ameliorates the effects of glycation consistent with cellular aging. Subsequent topical application of the compounds in skin models results in a reduction in glycation-induced AGEs, an increase in collagen expression and a stratification of the epidermis. Conclusion: Glycation could result in age-related alterations in the structural and cellular organizations of the superficial layers of the skin, which can be restored by Resveratrol derivatives, pointing to their promising capacities as bioactive ingredients in cosmetic products. Insight into the potential parameters affected by skin glycation could also serve as a reference for screening the bioactive molecules for cosmetic purposes.

Minicraniotomy Under Local Anesthesia and Monitored Sedation for the Operative Treatment of Uncomplicated Traumatic Acute Extradural Hematoma.

BACKGROUND: Major craniotomy is currently the de facto operative treatment for traumatic acute extradural hematoma (AEDH). This craniotomy, involving extensive scalp dissection (the trauma flap) and major cranial bone opening, can be impracticable in the remote regions of some Western countries, and even more so in the low-resource health systems of most developing countries. METHODS: We describe the surgical technique of minicraniotomy under local anesthesia plus monitored sedation as a much less invasive operative treatment for AEDH. The results of its use in a preliminary patient group are also presented. RESULTS: The procedure has been carried out in 10 consecutive patients (7 men), including an infant 4 months of age. The age range was 4 months to 56 years. The patients suffered varying severity of head injury, with a median Glasgow Coma Scale (GCS) score of 11 out of 15 (range, 4-15). The median trauma to surgery time was 25 hours (range, 13-192 hours). The surgery was successfully completed, with hematoma evacuated and hemostasis achieved. The median duration of surgery was 90 minutes. The in-hospital outcome was Glasgow Outcome Scale score of normal status in 6 patients, moderate deficit in 2 patients, and vegetative state in the patient whose preoperative GCS score was 4. One other patient, admitted with a GCS score of 11, died 5 days postoperatively from extracranial causes. The surviving patients have been followed-up for a median time of 15 months with no new deficits. CONCLUSIONS: Compared with full craniotomy under general anesthesia, minicraniotomy under local anesthesia plus sedation may be a more pragmatic, less invasive, and low-cost surgical treatment option for uncomplicated traumatic acute extradural hematoma.

Melanogenic Difference Consideration in Ethnic Skin Type: A Balance Approach Between Skin Brightening Applications and Beneficial Sun Exposure.

Human skin demonstrates a striking variation in tone and color that is evident among multiple demographic populations. Such characteristics are determined predominantly by the expression of the genes controlling the quantity and quality of melanin, which can alter significantly due to the presence of small nucleotide polymorphism affecting various steps of the melanogenesis process and generally linked to the lighter skin phenotypes. Genetically determined, constitutive skin color is additionally complemented by the facultative melanogenesis and tanning responses; with high levels of melanin and melanogenic factors broadly recognized to have a protective effect against the UVR-induced molecular damage in darker skin. Long-term sun exposure, together with a genetic makeup responsible for the ability to tan or the activity of constitutive melanogenic factors, triggers defects in pigmentation across all ethnic skin types. However, sun exposure also has well documented beneficial effects that manifest at both skin homeostasis and the systemic level, such as synthesis of vitamin D, which is thought to be less efficient in the presence of high levels of melanin or potentially linked to the polymorphism in the genes responsible for skin darkening triggered by UVR. In this review, we discuss melanogenesis in a context of constitutive pigmentation, defined by gene polymorphism in ethnic skin types, and facultative pigmentation that is not only associated with the capacity to protect the skin against photo-damage but could also have an impact on vitamin D synthesis through gene polymorphism. Modulating the activities of melanogenic genes, with the focus on the markers specifically altered by polymorphism combined with differential requirements of sun exposure in ethnic skin types, could enhance the applications of already existing skin brightening factors and provide a novel approach toward improved skin tone and health in personalized skincare.

DNA damage in human skin and the capacities of natural compounds to modulate the bystander signalling.

Human skin is a stratified organ frequently exposed to sun-generated ultraviolet radiation (UVR), which is considered one of the major factors responsible for DNA damage. Such damage can be direct, through interactions of DNA with UV photons, or indirect, mainly through enhanced production of reactive oxygen species that introduce oxidative changes to the DNA. Oxidative stress and DNA damage also associate with profound changes at the cellular and molecular level involving several cell cycle and signal transduction factors responsible for DNA repair or irreversible changes linked to ageing. Crucially, some of these factors constitute part of the signalling known for the induction of biological changes in non-irradiated, neighbouring cells and defined as the bystander effect. Network interactions with a number of natural compounds, based on their known activity towards these biomarkers in the skin, reveal the capacity to inhibit both the bystander signalling and cell cycle/DNA damage molecules while increasing expression of the anti-oxidant enzymes. Based on this information, we discuss the likely polypharmacology applications of the natural compounds and next-generation screening technologies in improving the anti-oxidant and DNA repair capacities of the skin.

Spinal extradural arachnoid cyst in a child-a case report.

Extradural spinal arachnoid cysts are rare lesions. They frequently communicate with the subarachnoid space through a defect in the dura. Symptoms result from compression of the spinal cord or nerve roots. The treatment of choice is complete surgical excision. We report the case of a 12-year-old girl with extradural spinal arachnoid cyst who had complete surgical excision with good outcome.

Challenging the myth of outpatient craniotomy for brain tumor in a Sub-Saharan African setting: A case series of two patients in Ibadan, Nigeria.

BACKGROUND: The concept of modern neuro-oncology hinges on strategic innovation and refinement of procedures with the intention to enhance safety, optimize extent of tumor resection, and improve not only survival but also the quality of life as well. One of such refinements includes same-day hospital admission, as well as early discharge following brain tumor surgeries. The latter has been further stretched to same-day discharge in particular settings to reduce the risk of nosocomial infections, cut brain tumor surgery costs, and improve patients' satisfaction. We highlight the challenges and possible benefits of outpatient craniotomy in a sub-Saharan African setting portrayed by the presence of lean resources and a predominant "out of pocket" health-care financing. CASE DESCRIPTION: Outpatient craniotomy was performed in two selected patients harboring intra-axial tumors: a right temporal low-grade glioma and a left frontal metastasis. The clinical outcome proved successful at short- and long-term in both patients; complications related to surgery and same-day discharge were not reported. CONCLUSION: Outpatient craniotomy is practicable and safe in resource-challenged environments and can further make brain tumor surgery cost effective and acceptable in carefully selected patients. Further prospective studies in similar settings but involving larger groups of patients are warranted.

Nigerian surgical outcomes - Report of a 7-day prospective cohort study and external validation of the African surgical outcomes study surgical risk calculator.

BACKGROUND: Surgical outcomes study for individual nations remains important because of international differences in patterns of surgical disease. We aimed to contribute to data on post-operative complications, critical care admissions and mortality following elective surgery in Nigeria and also validate the African Surgical Outcomes Study (ASOS) surgical risk calculator in our adult patient cohort. MATERIALS AND METHODS: We conducted a 7-day, national prospective observational cohort study in consented consecutive patients undergoing elective surgery with a planned overnight hospital stay following elective surgery during a seven-day study period. The outcome measures were in-hospital postoperative complications, critical care admissions and in-hospital mortality censored at 30 days. Also, we identified variables which significantly contributed to higher ASOS surgical risk score. External validation was performed using area under the receiver operating characteristic curve (ROC) for discrimination assessment and Hosmer-Lemeshow test for calibration. RESULTS: A total of 1,425 patients from 79 hospitals participated in the study. Postoperative complications occurred in 264(18.5%, 95% CI 16.6-20.6), 20(7.6%) of whom were admitted into the ICU and 16(6.0%) did not survive. Total ICU admission was 57 (4%), with mortality rate of 23.5% following planned admission and overall in-hospital death was 22(1.5%, 95% CI 0.9-2.2). All prognostic factors in the ASOS risk calculator were significantly associated with higher ASOS score and the scoring system showed moderate discrimination (0⋅73, 95% CI 0.62-0.83). Hosmer-Lemeshow χ2 test revealed scale was well calibrated in the validation cohort. CONCLUSION: NiSOS validates the findings of ASOS and the ability of the ASOS surgical risk calculator to predict risk of developing severe postoperative complications and mortality. We identified failure-to-rescue as a problem in Nigeria. Furthermore, this study has provided policy makers with benchmarks that can be used to monitor programmes aimed at reducing the morbidity and mortality after elective surgery. We recommend the adoption of the ASOS surgical risk calculator as a tool for risk stratification preoperatively for elective surgery.

Outcome of cranial surgery in Nigerian patients with hemoglobinopathies: A retrospective study.

BACKGROUND: Surgical intervention in patients with hemoglobinopathies has been extensively reviewed in the literature, but information on the outcome of cranial surgery in this patient population in sub-Saharan Africa is limited. METHODS: This is a retrospective study of patients with hemoglobinopathies, who underwent brain surgery in our facility. The review covered a 5-year period. We examined patient- and surgery-related variables and described the surgical complications as well as the 60-day mortality. RESULTS: A total of nine procedures (eight under general anesthesia and one under local anesthesia) were performed on seven patients with hemoglobinopathy during the study period. Eight (88.9%) of these were done in female patients and one (11.1%) in a male patient. Six (66.7%) were performed in patients with no previous history of blood transfusion. Hb SC accounted for five (55.6%), Hb SS for three (33.3%), and Hb CC for one (11.1%) procedure, respectively. Three (33.3%) of these procedures were brain tumor-related, three (33.3%) trauma-related, one (11.1%) cosmetic, one (11.1%) vascular, and one for a postoperative complication. Only one (11.1%) procedure was associated with preoperative blood transfusion, whereas there was a need for blood transfusion following five (55.6%) of the procedures. There was a mortality rate of 11.1% (1 case). Other complications were recorded after three (33.3%) of the procedures and none with five (55.6%) of the procedures. CONCLUSION: Neurosurgery is possible and safe in patients with hemoglobin disorders. Adequate preoperative preparation, proper anesthetic techniques, meticulous surgery, and excellent postoperative care can help optimize outcome of surgical intervention in this patient population.

Involvement of the nuclear structural proteins in aging-related responses of human skin to the environmental stress.

Human skin is a stratified endocrine organ with primary roles in protection against detrimental biochemical and biophysical factors in the environment. Environmental stress causes gradual accumulation of the macromolecular damage and clinical manifestations consistent with chronic inflammatory conditions and premature aging of the skin. Structural proteins of cell nucleus, the nuclear lamins and lamina-associated proteins, play an important role in the regulation of a number of signal transduction pathways associated with stress. The nuclear lamina proteins have been implicated in a number of degenerative disorders with frequent clinical manifestations of the skin conditions related to premature aging. Analysis of the molecular signatures in response of the skin to a range of damaging factors not only points at the likely involvement of the nuclear lamina in transmission of the signals between the environment and cell nucleus but also defines skin's sensitivity to stress, and therefore the capacities to counteract external damage in aging.

Personalized skincare: from molecular basis to clinical and commercial applications.

Individual responses of human skin to the environmental stress are determined by differences in the anatomy and physiology that are closely linked to the genetic characteristics such as pigmentation. Ethnic skin phenotypes can be distinguished based on defined genotypic traits, structural organization and compartmentalized sensitivity to distinct extrinsic aging factors. These differences are not only responsible for the variation in skin performance after exposure to damaging conditions, but can also affect the mechanisms of drug absorption, sensitization and other longer term effects. The unique characteristics of the individual skin function and, particularly, of the ethnic skin type are currently considered to shape the future of clinical and pharmacologic interventions as a basis for personalized skincare. Individual approaches to skincare render a novel and actively growing area with a range of biomedical and commercial applications within cosmetics industry. In this review, we summarize the aspects of the molecular and clinical manifestations of the environmental stress on human skin and proposed protective mechanisms that are linked to ethnic differences and pathophysiology of extrinsic skin aging. We subsequently discuss the possible applications and translation of this knowledge into personalized skincare.