Melasma pathogenesis: a review of the latest research, pathological findings, and investigational therapies

Melasma is an acquired hyperpigmentation disorder most commonly affecting females with darker skin types. It is triggered by several factors including sun exposure, genetic influences, and female sex hormones. The pathology of melasma extends beyond melanocytes and recent literature points to interactions between keratinocytes, mast cells, gene regulation abnormalities, neovascularization, and disruption of basement membrane. This complex pathogenesis makes melasma difficult to target and likely to recur post treatment. A better understanding of the latest pathological findings is key to developing novel and successful treatment options. This review aims to provide a summary of the more novel pathological findings and latest investigational therapies

Longitudinal monitoring of CA125 levels provides additional information about survival in ovarian cancer

<p>Abstract</p> <p>Background</p> <p>We investigated the prognostic impact of changes in serum CA125 levels during the first 3 months of therapy in ovarian cancer.</p> <p>Methods</p> <p>A case series of 170 ovarian cancer patients treated at Cancer Treatment Centers of America. Based on CA125 levels at baseline and 3 months, patients were classified into 4 groups: 1) Normal (0-35 U/ml) at baseline and three months; 2) High (>35 U/ml) at baseline, normal at three months; 3) Normal at baseline, high at 3 months; 4) High at baseline and three months. Kaplan Meier method was used to calculate survival across the 4 categories.</p> <p>Results</p> <p>Of 170 patients, 36 were newly diagnosed while 134 had received prior treatment. 25 had stage I disease at diagnosis, 15 stage II, 106 stage III and 14 stage IV. The median age at presentation was 54.2 years (range 23.1 - 82.5 years). At baseline, 31 patients had normal (0-35 U/ml) serum CA125 levels while 139 had high (>35 U/ml) levels. At 3 months, 59 had normal while 111 had high levels. Patients with a reduced CA125 at 3 months had a significantly better survival than those with increased CA125 at 3 months. Patients with normal values of CA125 at both baseline and 3 months had the best overall survival.</p> <p>Conclusions</p> <p>These data show that reduction in CA125 after 3 months of therapy is associated with better overall survival in ovarian cancer. Patients without a significant decline in CA125 after 3 months of therapy have a particularly poor prognosis.</p

Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology

<p>Abstract</p> <p>Background</p> <p>Serum 25-hydroxyvitamin D [25(OH)D] is the major circulating form of vitamin D and a standard indicator of vitamin D status. Emerging evidence in the literature suggests a high prevalence of suboptimal vitamin D (as defined by serum 25(OH)D levels of <32 ng/ml) as well as an association between lower serum levels and higher mortality in cancer. We investigated the effect of oral vitamin D supplementation as a means for restoring suboptimal levels to optimal levels in cancer.</p> <p>Methods</p> <p>This is a retrospective observational study of 2198 cancer patients who had a baseline test prior to initiation of cancer therapy at our hospital to evaluate serum 25(OH)D levels between Jan 08 and Dec 09 as part of their initial nutritional evaluation. Patients with baseline levels of < = 32 ng/ml (n = 1651) were considered to have suboptimal serum 25(OH)D levels and were supplemented with 8000 IU of Vitamin D3 (four 2000 IU D3 capsules) daily as part of their nutritional care plan. The patients were retested at their first follow-up visit. Of 1651 patients, 799 were available for follow up assessment. The mean serum 25(OH)D levels were compared in these 799 patients across the 2 time points (baseline and first follow-up) using paired sample t-test. We also investigated the factors associated with response to vitamin D supplementation.</p> <p>Results</p> <p>Of 2198 patients, 814 were males and 1384 females. 1051 were newly diagnosed and treated at our hospital while 1147 were diagnosed and treated elsewhere. The mean age at presentation was 55.4 years. The most common cancer types were breast (500, 22.7%), lung (328, 14.9%), pancreas (214, 9.7%), colorectal (204, 9.3%) and prostate (185, 8.4%). The mean time duration between baseline and first follow-up assessment was 14.7 weeks (median 10.9 weeks and range 4 weeks to 97.1 weeks). The mean serum 25(OH)D levels were 19.1 ng/ml (SD = 7.5) and 36.2 ng/ml (SD = 17.1) at baseline and first follow-up respectively; p < 0.001. Patients with prostate and lung cancer had the highest percentage of responders (70% and 69.2% respectively) while those with colorectal and pancreas had the lowest (46.7% each). Similarly, patients with serum levels 20-32 ng/ml at baseline were most likely to attain levels > 32 ng/ml compared to patients with baseline levels < 20 ng/ml.</p> <p>Conclusions</p> <p>The response to supplementation from suboptimal to optimal levels was greatest in patients with prostate and lung cancer as well as those with baseline levels between 20-32 ng/ml. Characteristics of non-responders as well as those who take longer to respond to supplementation need to be further studied and defined. Additionally, the impact of improved serum 25(OH)D levels on patient survival and quality of life needs to be investigated.</p

Efficacy of different oils used for the extraction of annatto colour from the seeds of Bixa orellana L.

Annatto, a naturally obtained colour is a potential and valuable Non Wood Forest Product (NWFP). It is obtained from the seeds of plant species Bixa orellana L. The present experiment was carried out to find the efficacy of different oils used for annatto colour extraction. Experiment was started with the pretreatment of seeds of B. orellana with soaking in water at 0%, 50%, 100% and 150% (v/w) for 24 hrs at room temperature and colour extraction with castor oil at 100°C showed that maximum bixin (%) was found from the pretreated seeds with 50% (v/w) water soaking i.e., 0.46% bixin. Similarly for oil soluble annatto extraction method, the maximum extraction of bixin (0.99 %) was found with castor oil at 120°C for 1 hr and least bixin (0.03 %) was recorded with mustard oil at 60oC temperature for 1 hr. Sesame oil and ground nut oil were also showed better extractability. Out of different treatments, castor oil at 120°C for 1 hr gave better result with respect to bixin extraction as compared to others

Can subjective global assessment of nutritional status predict survival in ovarian cancer?

<p>Abstract</p> <p>Background</p> <p>Malnutrition is a significant problem in patients with ovarian cancer. The goal of this study was to investigate the prognostic role of Subjective Global Assessment (SGA) in patients with ovarian cancer treated in an integrative cancer treatment setting.</p> <p>Methods</p> <p>We evaluated a case series of 132 ovarian cancer patients treated at Cancer Treatment Centers of America^®from Jan 2001 to May 2006. SGA was used to assess nutritional status at baseline. Using SGA, patients were classified as well nourished (SGA A), moderately malnourished (SGA B) or severely malnourished (SGA C). Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of SGA independent of other factors.</p> <p>Results</p> <p>Of 132 patients, 24 were newly diagnosed while 108 had received prior treatment. 15 had stage I disease at diagnosis, 8 stage II, 85 stage III and 17 stage IV. The median age at presentation was 54.4 years (range 25.5 – 82.5 years). 66 patients were well-nourished (SGA A), 35 moderately malnourished (SGA B) and 31 severely malnourished (SGA C). Well nourished patients had a median survival of 19.3 months (95% CI: 14.1 to 24.5), moderately malnourished 15.5 months (95% CI: 5.8 to 25.1), and severely malnourished 6.7 months (95% CI: 4.1 to 9.3); the difference being statistically significant (p = 0.0003). Multivariate Cox modeling, after adjusting for stage at diagnosis and prior treatment history found that moderately malnourished and severely malnourished status were associated with a relative risk of 2.1 (95% CI: 1.2 to 3.6, p = 0.008) and 3.4 (95% CI: 1.9 to 5.8, p < 0.001) respectively as compared to well nourished status.</p> <p>Conclusion</p> <p>Univariate and multivariate survival analyses found that low SGA scores (i.e. well-nourished status) are associated with better survival outcomes. This study lends support to the role of aggressive nutritional intervention in improving patient outcomes in cancer care.</p

Ethanolamines as corrosion inhibitors for zinc in (HNO3 + H2SO4) binary acid mixture

Abstract: This work deals with the study of corrosion behaviour for zinc in (HNO 3 + H 2 SO 4 ) binary acid mixture containing ethanolamines. Corrosion rate increases with concentration of acid and temperature. At constant acid concentration, the inhibition efficiency of ethanolamines increases with the inhibitor concentration. Value of ∆Ga increases and inhibition decreases with temperature. The mode of inhibition action appears to be chemisorption

Ovine multiparity is associated with diminished vaginal muscularis, increased elastic fibres and vaginal wall weakness: implication for pelvic organ prolapse

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Pelvic Organ Prolapse (POP) is a major clinical burden affecting 25% of women, with vaginal delivery a major contributing factor. We hypothesised that increasing parity weakens the vagina by altering the extracellular matrix proteins and smooth muscle thereby leading to POP vulnerability. We used a modified POP-quantification (POP-Q) system and a novel pressure sensor to measure vaginal wall weakness in nulliparous, primiparous and multiparous ewes. These measurements were correlated with histological, biochemical and biomechanical properties of the ovine vagina. Primiparous and multiparous ewes had greater displacement of vaginal tissue compared to nulliparous at points Aa, Ap and Ba and lower pressure sensor measurements at points equivalent to Ap and Ba. Vaginal wall muscularis of multiparous ewes was thinner than nulliparous and had greater elastic fibre content. Collagen content was lower in primiparous than nulliparous ewes, but collagen organisation did not differ. Biomechanically, multiparous vaginal tissue was weaker and less stiff than nulliparous. Parity had a significant impact on the structure and function of the ovine vaginal wall, as the multiparous vaginal wall was weaker and had a thinner muscularis than nulliparous ewes. This correlated with “POP-Q” and pressure sensor measurements showing greater tissue laxity in multiparous compared to nulliparous ewes

Renal Cell Carcinoma with Unusual Metastasis to the Small Intestine Manifesting as Extensive Polyposis: Successful Management with Intraoperative Therapeutic Endoscopy

We present here a rare clinical case of a 53-year-old gentleman with metastasis from renal cell carcinoma (RCC) to the small intestine presenting with extensive polyposis and massive gastrointestinal bleeding which was successfully managed with intraoperative endoscopic polypectomy and segmental small bowel resection. The patient presented with melena 2 weeks after right nephrectomy for RCC. Capsule endoscopy found extensive polyposis throughout the small bowel, and the histological features confirmed the diagnosis of metastatic RCC. The patient eventually underwent laparotomy with intraoperative endoscopy of the entire small bowel. Most of the polyps were removed by snare polypectomy. Three segments of the small bowel with extensive transmural involvement had to be resected with primary anastomosis. In the 2 months following his surgery, the patient had no further evidence of gastrointestinal bleeding. The decision of meticulously removing close to 100 polyps by intraoperative endoscopy prevented the patient from requiring total small bowel resection and lifelong dependence on parenteral nutrition. In conclusion, gastrointestinal bleeding in a patient with known RCC should always trigger full gastrointestinal work-up including capsule endoscopy and, if necessary, double balloon enteroscopy

Excess mortality in US Veterans during the COVID-19 pandemic: an individual-level cohort study.

BACKGROUND: Most analyses of excess mortality during the COVID-19 pandemic have employed aggregate data. Individual-level data from the largest integrated healthcare system in the US may enhance understanding of excess mortality. METHODS: We performed an observational cohort study following patients receiving care from the Department of Veterans Affairs (VA) between 1 March 2018 and 28 February 2022. We estimated excess mortality on an absolute scale (i.e. excess mortality rates, number of excess deaths) and a relative scale by measuring the hazard ratio (HR) for mortality comparing pandemic and pre-pandemic periods, overall and within demographic and clinical subgroups. Comorbidity burden and frailty were measured using the Charlson Comorbidity Index and Veterans Aging Cohort Study Index, respectively. RESULTS: Of 5 905 747 patients, the median age was 65.8 years and 91% were men. Overall, the excess mortality rate was 10.0 deaths/1000 person-years (PY), with a total of 103 164 excess deaths and pandemic HR of 1.25 (95% CI 1.25-1.26). Excess mortality rates were highest among the most frail patients (52.0/1000 PY) and those with the highest comorbidity burden (16.3/1000 PY). However, the largest relative mortality increases were observed among the least frail (HR 1.31, 95% CI 1.30-1.32) and those with the lowest comorbidity burden (HR 1.44, 95% CI 1.43-1.46). CONCLUSIONS: Individual-level data offered crucial clinical and operational insights into US excess mortality patterns during the COVID-19 pandemic. Notable differences emerged among clinical risk groups, emphasizing the need for reporting excess mortality in both absolute and relative terms to inform resource allocation in future outbreaks

Serum 25-hydroxyvitamin D is inversely associated with body mass index in cancer

<p>Abstract</p> <p>Background</p> <p>The association between vitamin D deficiency and obesity in healthy populations and different disease states remains unsettled with studies reporting conflicting findings. Moreover, current dietary recommendations for vitamin D do not take into account a person's body mass index (BMI). We investigated the relationship between serum 25-hydroxy-vitamin D [25(OH)D] and BMI in cancer.</p> <p>Methods</p> <p>A consecutive case series of 738 cancer patients. Serum 25(OH)D was measured at presentation to the hospital. The cohort was divided into 4 BMI groups (underweight: <18.5, normal weight: 18.5-24.9, overweight: 25-29.9, and obese: >30.0 kg/m²). Mean 25(OH)D was compared across the 4 BMI groups using ANOVA. Linear regression was used to quantify the relationship between BMI and 25(OH)D.</p> <p>Results</p> <p>303 were males and 435 females. Mean age at diagnosis was 55.6 years. The mean BMI was 27.9 kg/m²and mean serum 25(OH)D was 21.9 ng/ml. Most common cancers were lung (134), breast (131), colorectal (97), pancreas (86) and prostate (45). Obese patients had significantly lower serum 25(OH)D levels (17.9 ng/ml) as compared to normal weight (24.6 ng/ml) and overweight (22.8 ng/ml) patients; p < 0.001. After adjusting for age, every 1 kg/m²increase in BMI was significantly associated with 0.42 ng/ml decline in serum 25(OH)D levels.</p> <p>Conclusions</p> <p>Obese cancer patients (BMI >= 30 kg/m²) had significantly lower levels of serum 25(OH)D as compared to non-obese patients (BMI <30 kg/m²). BMI should be taken into account when assessing a patient's vitamin D status and more aggressive vitamin D supplementation should be considered in obese cancer patients.</p