Cutaneous Malignant Melanoma Incidences Analyzed Worldwide by Skin Type over Advancing Age of Males and Females: Evidence Estrogen and Androgenic Hair are Risk Factors

We previously analyzed cutaneous malignant melanoma (CMM) incidences worldwide by sex, age, and Fitzpatrick skin type over time (1955-2007) and found only European-ancestry populations have exponential increasing incidences and about a 2-log increase in the risk between the youngest age groups (0-14 and 15-29 yr). We proposed the increasing incidence over time may be from the spread of Human Papilloma Virus (HPV) found in CMM biopsies, and that the 2-log incidence increase between the youngest age groups might be from developing androgenic hair. The increasing incidence with age may be from white hairs transmitting UV radiation to follicular melanocytes. Here we analyzed CMM incidences over the advancing age of males and females of every skin type (I-VI) worldwide. We found only European-ancestry females have a linear increase in their CMM risk while males of all races have a power function increase in their risk with advancing age. We propose the gradual loss of HPV-infected androgenic follicles with advancing age of only European-ancestry females during and after menopause significantly reduces their CMM risk compared to all males who do not have significant estrogen loss and consequent loss of androgenic hair with advancing age. All other races have females with significantly lower amounts of androgenic body hair so that its loss with advancing age is not significant. These results combined with those in the literature and our previous findings showing CMM has been increasing over time, suggests estrogen synergizes HPV infection of androgenic follicular melanocytes significantly increasing the risk for getting CMM

Cutaneous Malignant Melanoma Incidences Analyzed Worldwide by Sex, Age, and Skin Type over Personal Ultraviolet-B Dose Shows No Role for Sunburn but Implies One for Vitamin D\u3csub\u3e3\u3c/sub\u3e

Because the incidence of cutaneous malignant melanoma (CMM) was reported to increase with increasing terrestrial UVR (290–400 nm) doses in the US back in 1975 and a recent publication showed no association exists with UVR exposure at all, we set out to fully elucidate the role of UVR in CMM. To achieve this goal, we analyzed the CMM incidences over latitude and estimated the average personal UVR dose in the US and numerous countries (\u3e 50) on 5 continents around the world. Using data from the International Agency for Research on Cancer in 2005, we performed worldwide analysis of CMM over UVR dose by sex, age group (0–14, 15–29, 30–49, 50–69, 70–85+) and Fitzpatrick skin types I-VI. Surprisingly, increasing UVR doses, which represent erythemally-weighted doses comprised primarily of UVB (290–315 nm) radiation, did not significantly correlate with increasing CMM incidence for people with any skin type anywhere in the world. Paradoxically, we found significant correlations between increasing CMM and decreasing UVB dose in Europeans with skin types I-IV. Both Europeans and Americans in some age groups have significant increasing CMM incidences with decreasing UVB dose, which shows UVB is not the main driver in CMM and suggests a possible role for lower cutaneous vitamin D3 levels and UVA (315–400 nm) radiation. CMM may be initiated or promoted by UVA radiation because people are exposed to it indoors through windows and outdoors through some sunscreen formulations. Thus, our findings may explain why some broad-spectrum sunscreen formulations do not protect against getting CM

Worldwide Cutaneous Malignant Melanoma Incidences Analyzed by Sex, Age, and Skin Type Over Time (1955–2007): Is HPV Infection of Androgenic Hair Follicular Melanocytes a Risk Factor for Developing Melanoma Exclusively in People of European-Ancestry?

The cutaneous malignant melanoma (CMM) incidence has been increasing in an exponential manner in certain populations around the world for over 7 decades. To help illuminate the etiology, we performed worldwide temporal (1955–2007) CMM incidence analysis by sex, age (0–14, 15–29, 30–49, 50–69, 70–85+), and skin type on 6 continents using data from the International Agency for Research on Cancer. We observe an exponential increase in the CMM incidence over time and an increase of about 2 orders of magnitude between age groups 0–14 and 15–29 exclusively in European-ancestry populations around the world independent of skin type (I–III or III–IV). Other populations like the Chinese (III-IV) had much lower CMM incidences that either remained stable or temporally decreased but did not display a dramatic increase between the youngest age groups. The dramatic increase in the incidence between the youngest age groups found only in European-ancestry populations suggests one of the most important risk factors for CMM may be developing androgenic hair, the occurrence of which appears to correlate with the distribution of CMM over male and female body sites. Besides that potential new risk factor, the increasing CMM incidence with increasing age, known not to be from cumulative UV doses, may be associated with age-related changes to skin, i.e., thinning epidermis causing lower vitamin D3 levels, and hair, i.e., whitening from higher reactive oxygen species. The temporal exponential increasing CMM incidence in European-ancestry populations may be due to Human Papilloma Virus infection of follicular hair melanocytes, found in CMM biopsies

Worldwide Cutaneous Malignant Melanoma Incidences Analyzed by Sex, Age, and Skin Type Over Time (1955–2007): Is HPV Infection of Androgenic Hair Follicular Melanocytes a Risk Factor for Developing Melanoma Exclusively in People of European-Ancestry?

The cutaneous malignant melanoma (CMM) incidence has been increasing in an exponential manner in certain populations around the world for over 7 decades. To help illuminate the etiology, we performed worldwide temporal (1955–2007) CMM incidence analysis by sex, age (0–14, 15–29, 30–49, 50–69, 70–85+), and skin type on 6 continents using data from the International Agency for Research on Cancer. We observe an exponential increase in the CMM incidence over time and an increase of about 2 orders of magnitude between age groups 0–14 and 15–29 exclusively in European-ancestry populations around the world independent of skin type (I–III or III–IV). Other populations like the Chinese (III-IV) had much lower CMM incidences that either remained stable or temporally decreased but did not display a dramatic increase between the youngest age groups. The dramatic increase in the incidence between the youngest age groups found only in European-ancestry populations suggests one of the most important risk factors for CMM may be developing androgenic hair, the occurrence of which appears to correlate with the distribution of CMM over male and female body sites. Besides that potential new risk factor, the increasing CMM incidence with increasing age, known not to be from cumulative UV doses, may be associated with age-related changes to skin, i.e., thinning epidermis causing lower vitamin D3 levels, and hair, i.e., whitening from higher reactive oxygen species. The temporal exponential increasing CMM incidence in European-ancestry populations may be due to Human Papilloma Virus infection of follicular hair melanocytes, found in CMM biopsies

Altered differential control of sympathetic outflow following sedentary conditions: Role of subregional neuroplasticity in the RVLM

Despite the classically held belief of an “all-or-none” activation of the sympathetic nervous system, differential responses in sympathetic nerve activity (SNA) can occur acutely at varying magnitudes and in opposing directions. Sympathetic nerves also appear to contribute differentially to various disease states including hypertension and heart failure. Previously we have reported that sedentary conditions enhanced responses of splanchnic SNA (SSNA) but not lumbar SNA (LSNA) to activation of the rostral ventrolateral medulla (RVLM) in rats. Bulbospinal RVLM neurons from sedentary rats also exhibit increased dendritic branching in rostral regions of the RVLM. We hypothesized that regionally specific structural neuroplasticity would manifest as enhanced SSNA but not LSNA following activation of the rostral RVLM. To test this hypothesis, groups of physically active (10–12 weeks on running wheels) or sedentary, male Sprague-Dawley rats were instrumented to record mean arterial pressure, LSNA and SSNA under Inactin anesthesia and during microinjections of glutamate (30 nl, 10 mM) into multiple sites within the RVLM. Sedentary conditions enhanced SSNA but not LSNA responses and SSNA responses were enhanced at more central and rostral sites. Results suggest that enhanced SSNA responses in rostral RVLM coincide with enhanced dendritic branching in rostral RVLM observed previously. Identifying structural and functional neuroplasticity in specific populations of RVLM neurons may help identify new treatments for cardiovascular diseases, known to be more prevalent in sedentary individuals

Exponentially Increasing Incidences of Cutaneous Malignant Melanoma in Europe Correlate with Low Personal Annual UV Doses and Suggests 2 Major Risk Factors

For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

CAN CLINICAL EVALUATION BY PHYSIOTHERAPIST FORMS EARLY DETECTION OF BREAST CARCINOMA?

Introduction: Modern living associated with greater health hazards including cancers. Among which breast carcinoma ranks with higher prevalence in adult women. Physical laboratory investigations and screening. Early identification to a larger extent can influence better outcome and longevity especially for breast cancer subjects. Objectives: As physical therapist frequently involved in treating neck and low back ache as first contact healthcare expert, this research highlights importance of patients with chronic neck pain to be screened for lymph nodes, other related complaints like stiff neck, increasing atrophy, constant continuous pain, most of these could be related to malignancy while these subjects can be referred to physician or oncologist for to be detected and treated with due medical care for an enhanced post onco-surgical living standard. Materials and methods: 59-year-old diabetic subject with chronic continuous neck pain with nodules over posterior cervical spine was referred to undergo mammography by physiotherapist through physician. She was diagnosed later with hyper metabolic malignant lesion of left breast and underwent modified left radical mastectomy. Later, she was getting treated for her physical functioning in improving QOL were discussed with due evidence for the period 2020 to 2022. Results: With lesser follow up post mastectomy and early identification by physiotherapists remain key component of this research. Findings of this research can form foundation of onco physiotherapy in early clinical screening and referral to medical expert. Conclusions: If adhered can become novel means of physiotherapy evaluation as red flag and could be included in every patient physical evaluation in future

Ab initio and density functional theory based studies on collagen triplets

An understanding of the amino acid sequence dependent stability of polypeptides is of renowned interest to biophysicists and biochemists, in order to identify the nature of forces that stabilize the three-dimensional structure of proteins. In this study, the role of various collagen triplets influencing the stability of collagen has been addressed. It is found from this study that proline can stabilize the collagen triplet only when other residues are also in the polyproline II conformation. Solvation studies of various triplets indicate that the presence of polar residues increases the free energy of solvation. Especially the triplets containing arginine residues displays a higher solvation free energy. The chemical hardness of all the triplets in collagen-like conformation has been found to be higher than that in the extended conformation. Studies on Gly–X–Y, Gly–X–Hyp, and Gly–Pro–Y triplets confirm that there will be local variations in the stability of collagen along the entire sequence

Stabilization of collagen using plant polyphenol: role of catechin

Collagen, a unique connective tissue protein finds extensive application as biocompatible biomaterial in wound healing, as drug carriers, cosmetics, etc. A work has been undertaken to study the stabilization of type I collagen using the plant polyphenol catechin. Catechin treated collagen fibres showed a shrinkage temperature around 70°C implying that catechin is able to impart thermal stability to collagen. Catechin treated collagen fibres has been found to be stable even after treatment with high concentration of the secondary structural destabilizer, urea. Circular dichroism studies revealed that there is no major alteration in the structure of collagen on treatment with catechin. The study has demonstrated the involvement of hydrogen bonding and hydrophobic interactions as the major forces involved in the stabilization of collagen by the plant polyphenol, catechin