Natural History Research Articles

Natural history in Malan syndrome: survey of 28 adults and literature review

BackgroundMalan syndrome (MALNS), previously referred to as “Sotos syndrome 2” due to its resemblance to Sotos syndrome (SS), is an ultra-rare neurodevelopmental disorder characterized by overgrowth, typical craniofacial features, intellectual disability (ID), and a range of psychobehavioral, musculoskeletal, vision and neurological signs. As MALNS and SS partly overlap, it is essential to more accurately profile their clinical presentations and highlight their differences in order to improve syndrome specific management. An increasing number of individuals with MALNS reach adult-age though the natural history of the disorder is poorly characterized due to the small number of adult individuals described so far. As a consequence, current guidelines are limited to the pediatric population. Further delineation of MALNS is essential to optimize care in adulthood.ResultsA mixed approach based on cross-sectional data collection with a survey disseminated to caregivers of adults with molecularly confirmed MALNS and literature review was conducted. Twenty-eight caregivers completed the survey. Clinical presentation in adulthood is multisystemic and defined by psychobehavioral comorbidities (96%), musculoskeletal involvement (96%), vision impairment (96%) and neurological complications (86%). The most common signs were anxiety (79%), hypotonia (75%), movement difficulty (75%), scoliosis (64%), problems with coordination (61%), strabismus (57%), constipation (54%), breastbone abnormalities (54%) and advanced bone age during childhood (54%). Impaired vision was complicated by vision decline (36%) and optic atrophy (32%). We report some previously unidentified features, including high pain threshold (46%), incontinence (25%), tremors (21%), muscle hypoplasia (18%) and tics (18%).ConclusionsThis survey in the adult population has allowed a more complete description of the natural history of MALNS. Our findings will contribute to the development and improvement of standards of care for adults with MALNS to assure optimal health monitoring and treatment of evolutive complications. We propose additional recommendations to the previous dataset of clinical evaluations specifically applied to adults. The comparison of MALNS and SS adult presentation highlights significant differences in terms of prevalence and severity of ID, behavioral issues, and vision problems, confirming that a proper differential diagnosis between the two conditions is indispensable to guide physicians and mental health professionals to syndrome specific management.

Scenarios for the long-term efficacy of amyloid-targeting therapies in the context of the natural history of Alzheimer's disease.

Recent clinical trials of amyloid beta (Aβ)-targeting therapies in Alzheimer's disease (AD) have demonstrated a clinical benefit over 18 months, but their long-term impact on disease trajectory is not yet understood. We propose a framework for evaluating realistic long-term scenarios. Results from recent phase 3 trials of Aβ-targeting antibodies were integrated with an estimate of the long-term patient-level natural history trajectory of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score to explore realistic long-term efficacy scenarios. Three distinct long-term efficacy scenarios were examined, ranging from conservative to optimistic. These extrapolations of positive phase 3 trials suggested treatments delayed onset of severe dementia by 0.3 to 0.6 years (conservative), 1.1 to 1.9 years (intermediate), and 2.0 to 4.2 years (optimistic). Our study provides a common language for long-term impact of disease-modifying treatments. Our work calls for studies with longer follow-up and results from early intervention trials to provide a comprehensive assessment of these therapies' true long-term impact. We present long-term scenarios of the efficacy of AD therapies. In this framework, scenarios are defined relative to the natural history of AD. Long-term projections with different levels of optimism can be compared. It provides a common language for expressing beliefs about long-term efficacy.

Distribution, morphology, and natural history observations of the Colombian weasel, Neogale felipei

ABSTRACT The Colombian weasel, Neogale felipei, is a rare carnivoran known only from nine localities, eight in Colombia and one in Ecuador. Recent records have expanded our understanding of the distribution and threats that this mammal faces, but the species is still among the rarest Neotropical carnivores. Here, we present an update to the distribution of N. felipei based on a recent record obtained in the Cordillera Occidental (Western Cordillera) of Colombia, and information on internal and external morphology using noninvasive technique such as X-rays of museum preserved specimens. We also documented the presence of lice, Neotrichodectes minutus, which is the first documented ectoparasite of the species. With the new records, the species is currently known from 12 localities (11 in Colombia and one in Ecuador). We also present the first radiographic analyses for N. felipei and the obtained vertebral formula (49 total vertebrae) fits into the range reported for the species and other mustelids. Considering that the Colombian weasel is one of the rarest carnivores of the Neotropics, our work represents a noteworthy contribution to several aspects of the anatomy, distribution, and natural history of this rare carnivoran.

Pediatric meniscal surgery in Italy: A 10-year epidemiological nationwide registry study

PurposeOver the last two decades the incidence of meniscal injuries has grown amongst the pediatric population predominantly due to greater involvement in sporting activities. The treatment and the natural history represent a socioeconomic burden for healthcare systems. This study demonstrates the epidemiology of meniscal tears treated surgically in Italy from 2010 to 2019 in a population up to 18 years. MethodsData was collected from the National Archive of Hospital Discharges. ICD9-CM classification was used to select surgically treated meniscal injuries. Concomitant treatment of associated lesions were excluded. Data on the national population was retrieved from the Italian National Institute for Statistics (ISTAT). Statistical analyses were performed. Results17,449 isolated meniscal tears were surgically treated with a mean incidence of 20.6 per 100.000 in the Italian population aged up to 18 from 2010 to 2019. The mean age of patients was 15.85 with 89 % aged 14 or older. 30 % of the population was female. The incidence of medial meniscal surgery was higher than for the lateral meniscus. A declining trend in surgical incidence was observed. The mean hospitalization time was 1.53 days. ConclusionsOur study reveals a reduction in the total number of surgeries performed over the time frame and a significant rise in the incidence of meniscal lesions in pediatric patient above at the age of 13, especially in males. Despite a worldwide shift towards meniscal preservation, this trend is not evident in Italy as the current ICD9-CM classification does not differentiate between meniscectomy and meniscal repair, although an overall reduction in surgery may imply better management. Study designCohort study; Level of evidence III.

Legal regulation of the activities of Soviet and party bodies in the fight against the fascist-nationalist underground in the Baltic States (1944-1953)

The relevance is due to the theoretical and practical significance of scientific problems related to the study of the legal regulation of the activities of Soviet and party bodies in the fight against the fascist-nationalist underground in the Baltic States in the last years of the Great Patriotic War and the post-war years. The experience of fighting nationalism in the post-war decade, when the Soviet state managed to cope with the fascist-nationalist underground in a relatively short time, seems instructive at the present time.Purpose. Сlarification in the historical and legal aspect of the peculiarities of the struggle of Soviet and party organs, as well as organs and troops of the NKVD-NKGB of the USSR with the fascist-nationalist underground in the Baltic States in 1944-1953.Objectives: to analyze the main normative legal documents regulating the fight against the fascist-nationalist underground in the Baltic States in 1944-1953; to determine the features of the counteraction of Soviet and party organs, organs and troops of the NKVD-NKGB to the activities of participants in the fascist-nationalist underground in Lithuania, Latvia and Estonia in the last years of the Great Patriotic War and the first decade after the end of the war.Methodology. The dialectical, historical, comparative legal method was used as the methodological basis of the study due to the historical and legal nature of the article.Results the research was of a historical and legal nature and made it possible to identify the specifics of the activities of the Soviet authorities in the fight against the fascist-nationalist underground in the Baltic States. Not only operational-Chekist, military operations were carried out, but also criminal and repressive measures were carried out, but also administrative, agitation and propaganda measures corresponding to the "current moment" were applied. The struggle against the fascist-nationalist underground was led by party and Soviet bodies, both at the republican and all-Union levels.Conclusion. The complex of measures carried out in 1944-1953 in order to combat the fascist-nationalist underground in the Baltic States has historical and legal significance. The experience of its implementation can be used by the troops of the National Guard of the Russian Federation, state security agencies and other law enforcement agencies, both now and in the future, including as part of a special military operation.

Analysis of the order of marriage in Russia (based on the materials of the Pilot book)

The relevance of the research is determined by the fact that, based on the analysis of the Pilot Book, knowledge about the genesis of ancient Russian family law is expanding, allowing to reveal the historical roots of modern legislation in this area and to identify the influence of cultural, religious and social factors on the formation of norms and principles of family law. The scientific discussion on this issue contributes to a deep understanding of the history of the Russian state and law, the actualization of issues of marriage and family relations in the context of modern challenges and changes in society.The purpose of the study is to reveal the features, conditions and procedure of marriage in Russia.The objectives are to identify the factors influencing the order of marriage, identify obstacles to marriage, and establish the religious and legal basis of marital and family relations.Methodology. The methodological basis is determined by the historical and legal nature of the research, based on the principles of historicism, a systematic approach and objectivity in understanding the legacy of the Pilot Book.Results. In the course of the study, the foundations of family legislation were determined, among them are: the chaste nature of premarital relations, which does not violate the foundations of family values and life in marriage; the definition of marriage as a union of a man and a woman, with the aim of legitimate childbearing and avoiding a sinful life; the consent of both spouses to marry, the absence of obstacles to marriage (kinship, nepotism, etc.); the obligatory wedding of the spouses and the blessing of the priest of the couple; the responsibility of the husband for the wife.Conclusion. In the conditions of modern Russia, the appeal to the historical and legal heritage of the past is dictated by the need to strengthen the authority and support the institution of the family and basic family values. The analysis of the norms of the Steering Book (Nomocanon), which laid the foundations of family legislation, helps to understand the values and principles that have been formed in society over the centuries and influence modern legislation.

Characterizing the journey of Rett syndrome among females in the United States: a real-world evidence study using the Rett syndrome natural history study database

BackgroundWith the advent of the first targeted therapy for Rett Syndrome (RTT), a comprehensive assessment of the journey of RTT is needed to elucidate on present unmet needs in this population. This study characterized females with RTT in the United States and their disease journey with respect to longitudinal treatment patterns, RTT-related outcomes, and changes in disease severity.MethodsThis retrospective cohort study used registry data of females with RTT from the 5211 RTT Natural History Study (RNHS) (November 2015–July 2021). Pharmacological and supportive therapy use, RTT-related outcomes, and RTT severity, as measured by the Clinical Severity Scale and Motor Behavioral Assessment scale, were evaluated following the first RNHS visit. Analyses were conducted overall and in subgroups by RTT type (classic and atypical RTT) and age at first visit (pediatric and adult).ResultsA total of 455 females with RTT were included in the study, of whom 90.5% had classic RTT and 79.8% were pediatric individuals. Over a median follow-up of 4 years, use of pharmacological therapies, including prokinetic agents (42.7% vs. 28.3%), and supportive therapies, including physical therapy (87.3% vs. 40.2%) and speech-language therapy (86.8% vs. 23.9%), were more common in pediatric than adult individuals (all p < 0.05). Nearly half (44.6%) of all individuals had a hospital or emergency room visit, with a higher proportion of visits in individuals with classic RTT than atypical RTT and pediatric than adult individuals (both p = 0.001). An increasing trend in clinical severity was observed in pediatric individuals (mean change per year: 0.24; 95% confidence interval [CI]: 0.03, 0.44), while an increasing trend in motor-behavioral dysfunction was observed in pediatric individuals (mean change per year: 1.12; 95% CI: 0.63, 1.60) and those with classic RTT (mean change per year: 0.97; 95% CI: 0.53, 1.41).ConclusionsFindings from this study highlight the considerable burden of RTT across disease subtype and age. Despite reliance on supportive therapies and healthcare encounters, individuals with RTT experience increasing disease severity and motor-behavioral dysfunction in childhood and adolescence, underscoring the unmet needs of this population and the value of early intervention to manage RTT in the long-term.

Infantile hemangiomas: a dermatologist's perspective.

Infantile hemangioma (IH), the most common vascular tumor in pediatrics, is thought to arise from aberrant stem cell responses to stimuli such as hypoxia. This review explores the diverse manifestations, complications, and management strategies for IH, emphasizing the importance of a multidisciplinary approach. The epidemiology and risk factors associated with IH, including connections to prematurity, low birth weight, and family background, are discussed. The intricate pathogenesis involving hemangioma stem cells, KIAA1429, hypoxia, and the renin-angiotensin system is examined. The natural history and clinical features, as well as extracutaneous involvements such as hepatic IH, PHACES syndrome, and LUMBAR syndrome, are detailed. Complications such as ulceration, functional impairment, hypothyroidism, and cosmetic concerns are highlighted. The differential diagnosis and diagnostic modalities, including colorimeters, high-frequency ultrasonography, and imaging techniques, are discussed. Management approaches, including the use of propranolol, atenolol, corticosteroids, alternative systemic treatments, topical therapy, laser therapy, and surgery, are comprehensively reviewed. The evolving landscape of IH management is underscored, with ongoing research exploring alternative treatments and individualized approaches based on IH characteristics.

The genocidal disruption of Johannes Jacob Manissadjian’s (1862–1942) lifework: a biographical approach to mass violence and indigenous knowledge production

ABSTRACT Relying on a biographical approach that reconstructs the life and work of Johannes [Hovhanness/Յովհաննէս] Jakob [Hagop/Յակոբ] Manissadjian [Manisacıyan/Մանիսաճեան] (1862–1942), a highly successful scientist at the Anatolia College (Merzifon/Marsovan/Մարզվան), who established a meteorological station and a natural history museum with an extensive collection of specimens, the paper traces the routes of disappearance, dispersal and ruination of indigenous lives, people, and knowledge within the context of the Armenian genocide. Drawing on documents from Ottoman, German, and American archives, I stress the potential of biographical methods to study the processes and structures of mass violence targeting the Ottoman Armenians, as well as to foreground the agency and subjectivity of genocide survivors. The article also focuses on post-genocide scientific (dis)engagements of Manissadjian in light of Theodor W. Adorno’s ‘after Auschwitz’ discussions and from the perspective of indigenous knowledge production. In particular, his two ‘archival acts’ in the post-genocide context, the ‘Catalogue’ of the collection of the Anatolia College Museum that he prepared as ‘the former Curator’ and his small pamphlet entitled Proverbs of Turkey, which provided an ethnographic portrait of Anatolia, were his humble acts of saving a treasure trove of knowledge that was in danger of becoming debris.

Splenic complications in pediatric sickle cell disease: A retrospective cohort review.

To delineate the natural history of splenic complications other than loss of splenic function in children with sickle cell disease (SCD), we performed a retrospective chart review of patients with SCD treated at the Texas Children's Hospital. We determined the dates of diagnoses of splenic complications, the number of acute splenic sequestration crises (ASSC), and hydroxyurea treatment in pediatric patients with SCD. We also examined the association of hydroxyurea therapy with the onset and severity of ASSC. The cumulative prevalence of splenic complications was 24.7% for splenomegaly, 24.2% for ASSC, 9.6% for hypersplenism, and 5.6% for splenectomy. The cumulative prevalence of splenic complications was highest in patients with hemoglobin Sβ0 (69.2%), intermediate in hemoglobin SS (33.3%), low in hemoglobin SC (9.0%), and non-existent in hemoglobin Sβ+. The overall event rate of ASSC was 8.3 per 100 patient-years. The event-rate was 28.4 for hemoglobin Sβ0, 10.9 for hemoglobin SS, and 3.5 for hemoglobin SC. Patients with hemoglobin SS and hemoglobin Sβ0 on hydroxyurea therapy had a significantly higher occurrence of ASSC than those who were not, with event rates of 14.2 and 3.1, respectively. The event rate was also higher for children who started hydroxyurea before age 2years than for those who started after this age (19.8 and 9.2, respectively). The prevalence and severity of splenic problems vary widely between different sickle cell genotypes, with hemoglobin Sβ0 having the most severe complications. Hydroxyurea therapy is associated with increased incidence of ASSC, particularly when initiated before 2years of age.

Editorial Comment on “Natural History of Artificial Urinary Sphincter Erosion: Long-term Lower Urinary Tract Outcomes and Incontinence Management”

Editorial Comment on “Natural History of Artificial Urinary Sphincter Erosion: Long-term Lower Urinary Tract Outcomes and Incontinence Management”

Dilution of humoral immunity: Results from a natural history study of healthy total knee arthroplasty patients.

The incidence of prosthetic joint infection (PJI) following elective primary total knee arthroplasty (TKA) is very low but serious risk remains. To identify unknown risk factors, we completed a natural history study of IgG specific forStaphylococcus aureus antigens previously phenotyped as protective (anti-Atl) and pathogenic (anti-Isd). Twenty-five male and 25 female optimized patients 50-85 years of age and BMI 24-39 undergoing primary TKA were prospectively enrolled. Blood sampling was performed preoperatively, postoperative Day 1, and at 2, 6, and 12 weeks, to assess serum cytokine, anti-staphylococcal IgG levels and anti-tetanus toxoid IgG measured via custom Luminex assay. Clinical, demographic, and PROMIS-10 data were collected with outcomes to 2 years postop. All participants completed the study and 2-year follow-up. No patients were readmitted or noted to develop a surgical site infection or serious adverse event, and patient-reported outcomes were improved. Serology revealed a highly significant decrease in six out of eight antibody titers against specific S. aureus antigens on Day 1 (p < 0.0001), five of which normalized to preoperative levels within 2 weeks. These changes were commensurate with a decrease and recovery of anti-tetanus toxoid titers, and a 20% drop in hemoglobin 13.8 ± 1.7 at preop to 11.1 ± 1.8 mg/dL on Day 1 (p < 0.0001). After TKA, a significant decrease in humoral immunity commensurate with blood loss and hemodilution was recorded. This decrease in circulating anti-staphylococcal antibodies in the early postop period may represent a periprosthetic joint infection risk factor for patients.

Prediction of differential Gag versus Env responses to a mosaic HIV-1 vaccine regimen by HLA class I alleles.

HLA class I variation has the strongest effect genome-wide on outcome after HIV infection, and as such, an understanding of the impact of HLA polymorphism on response to HIV vaccination may inform vaccine design. We sought HLA associations with HIV-directed immunogenicity in the phase 1/2a APPROACH vaccine trial, which tested vaccine regimens containing mosaic inserts in Ad26 and MVA vectors, with or without a trimeric gp140 protein. While there were no HLA allelic associations with the overall cellular immune response to the vaccine assessed by ELISpot (Gag, Pol, and Env combined), significant associations with differential response to Gag compared to Env antigens were observed. Notably, HLA class I alleles known to associate with disease susceptibility in HIV natural history cohorts are associated with stronger Env-directed responses, whereas protective alleles are associated with stronger Gag-directed responses. Mean viral loads determined for each HLA allele in untreated individuals correlated negatively with the strength of the Gag response minus the Env response in Black vaccinees based on both ELISpot and CD8+ T cell ICS responses. As the association of T cell responses to conserved Gag epitopes with lower viral load in untreated individuals is well established, our data raise the possibility that the Ad26.Mos.HIV vaccine may induce more effective cellular responses in those with HLA alleles that confer improved virologic control in untreated HIV infection.IMPORTANCENo vaccine tested to date has shown sufficient efficacy against HIV infection. A vaccine that induces robust responses in one individual may fail to do so in another individual due to variation in HLA class I genes, loci central to the immune response. Extensive data have shown the strong effect of HLA variation on outcome after HIV infection, but very little is known about the effect of such variation on HIV vaccine success. Here, we identify a link between the effect of HLA variation on HIV disease outcome and immune responses to an HIV vaccine. HLA variants associated with better HIV control after infection also induce stronger responses against the HIV Gag protein relative to the Env protein after vaccination. Given the virologic control conferred by responses to Gag in natural history of HIV infection, these data suggest that HLA alleles conferring protection after HIV infection may also support a more effective cellular response to HIV vaccination.

IPINeT Ped-unPAD Study: Goals, Design, and Preliminary Results

Background: An unclassified primary antibody deficiency (unPAD) is a widely heterogeneous clinical entity, recently identified within the spectrum of Inborn Errors of Immunity (IEIs). Since unPAD has been traditionally considered as a mild condition, it has incorrectly received little attention, resulting in the paucity of extensive and comparable studies describing its natural history. To address the gaps in characterizing, understanding, and managing pediatric unPAD patients, the Italian Primary Immunodeficiency Network (IPINet) Ped-unPAD study has recently been launched. Methods: Seventeen IPINeT Centers have expressed interest to participate, and data collection is still on-going. Hereby, we anticipate preliminary key issues emerging from the first 110 enrolled patients, attending three IPINet Centers. Results: A proportion of unPAD patients have experienced a severe infectious phenotype, which required hospitalization in a quarter of patients and antibiotic prophylaxis or Immunoglobulin Replacement Therapy in approximately 10% of patients. In this partial cohort, a mean follow-up (FU) of 5 years confirmed unPAD diagnosis in fifty percent of cases, with the remaining being reclassified as the Transient Hypogammaglobulinemia of Infancy (25%) and other IEIs (25%), such as a Common Variable Immunodeficiency, Selective IgA deficiency, Selective IgM deficiency, and IgG3 subclass deficiency. Conclusions: Despite a phenotype overlap at diagnosis, clinicians should be aware that unPAD is a mutable condition that deserves comprehensive evaluation and long-term monitoring to dissect the final diagnosis for optimal treatment.

Diversity and ecological relationships of Cestoda and Monogenea parasites of freshwater stingrays (Myliobatiformes, Potamotrygonidae), in the upper Paraná River, Brazil.

The Neotropical freshwater stingrays of Potamotrygon genus present a unique and complex natural history and biogeographical pattern that can be traced to a marine origin and the colonization of the continental environment during the Miocene. During the evolution of potamotrygonids, several species of the parasitic fauna coevolved and co-opted concomitantly to their hosts during the colonization of the new environments. One striking example can be observed during the colonization of the upper Paraná River region. However, few studies explored the ecological and taxonomic aspects of potamotrygonid parasites. In this work, we investigate aspects of the ecology and taxonomy of the species of Monogenea and Cestoda that are parasites the species of freshwater stingrays of the genus Potamotrygon in the upper Paraná River. Our results indicate that at least six species of parasites are present in potamotrygonids in the region. Two of the observed parasites are putative new species and three of the parasitic species were identified for the first time in the region, hence expanding their geographic distributions. We quantified ecological aspects at different levels of communities for the collected parasite species. We compared the diversity in different locations and hosts and performed an exploratory analysis to investigate the differences in parasite abundance. Additionally, an identification key for the Monogenea and Cestoda species of the sampled region is provided.

Unraveling olfactory subtypes in Parkinson's disease and their effect on the natural history of the disease.

Hyposmia in Parkinson's disease (PD) had been studied before but had not been detailed by its temporal progression. This study observed how each olfactory subtype evolved in terms of motor symptoms, cardiac sympathetic innervation, and cognition. Two hundred and three early PD patients were classified as normosmia, hyposmia-converter (hypo-converter), and hyposmia. Their presynaptic monoamine availability at the time of diagnosis was assessed by positron emission tomography imaging using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and compared across the subtypes. Motor symptoms were evaluated in all patients, cardiac denervation was examined in 183 patients, and cognition in 195 patients were assessed using a neuropsychological battery. The domains were re-assessed 2-4 times, and the longitudinal data were analyzed to discern the natural course of each subtype. Twenty-nine (14.3%) patients belonged to the normosmia group, 34 (16.7%) to the hypo-converter group, and the rest to the hyposmia (69.0%) group. 85.7% of the total population became hyposmic during an average 3years of follow-up. The baseline motor symptoms, cardiac denervation, and cognition were comparable across the olfactory subtypes. Across the subtypes, a decline in the presynaptic monoamine densities of the caudate, especially the ventral-anterior subdivisions, correlated inversely with olfaction dysfunction. Over time, motor and cardiac denervation burdens worsened regardless of olfactory subtypes, but hypo-converters experienced faster cognitive deterioration than the other two groups. The results suggest that the olfactory subtypes have differential significance along the disease course, which might reflect the involvement of different neuro-biochemical circuitries.

Prevalence and characteristics of osseous bridging between vertebral bodies in the cervical spine: A skeletal study.

Osseous bridging (OB) in three or more segments of motions (SOMs) of the mobile spine was initially defined as diffuse idiopathic skeletal hyperostosis (DISH), located particularly in the thoracic spine (T-spine). This pathological phenomenon is often characterized by calcification and ossification, which take place simultaneously or separately. The soft tissues, mainly ligaments and entheses, are calcified, with bone formation not originating from the anterior longitudinal ligament (ALL). DISH formation can involve osteophytes, which are created by the ossification process and can involve soft tissue such as the ALL. The ALL can also be calcified. Until recently, the prevalence of DISH in the general population was considered low (0%-5%) and rare in the cervical spine (C-spine). In a cross-sectional observational skeletal study, we investigated the prevalence and location of C-spine OB between vertebral bodies with fewer than three SOMs. We tested a large sample (n = 2779) of C-spines housed in the Cleveland Museum of Natural History (Ohio, USA). The human sources of the samples had died between the years 1912 and 1938 and represented both sexes and two different ethnic groups: Black Americans and White Americans. The process development can be seen on the ALLs as calcification, osteophytosis, and candle-shaped. Among all of the specimens, 139 (5%) were affected by OB, mostly in one SOM. Prevalence tended to be higher in women, White Americans, and the older age group. The levels most affected were C3-C4, followed by C2-C3 and subsequently, C5-C6. OB involving two consecutive SOMs was found only at C5-C7. We believe it is important to respond to the presence of a single SOM with a presumptive diagnosis of OB and to follow up, identify whether the diagnosis is correct, and take preventive action if possible. There is a need for updated diagnostic criteria and research approaches that reflect contemporary lifestyle factors and their impact on spine health.

Retinal sensitivity in macular subfields and their association with contrast sensitivity in early and intermediate age-related macular degeneration.

Purpose To evaluate retinal sensitivity in subfields and its association with the novel quick contrast sensitivity function (qCSF) in patients with early age-related macular degeneration (eAMD), in patients with intermediate AMD (iAMD), and in healthy controls. Methods In this prospective longitudinal study retinal sensitivity of a customized 24-point grid was assessed by microperimetry Macular Integrity Assessment (MAIA, CenterVue, Padova, Italy) and divided into different subfields. The Multiple Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA) was used for qCSF testing. Linear models were used to test the association of functional metrics with variables of interest. Results 92 study eyes from 92 participants were analyzed (13 eAMD, 31 iAMD, and 48 controls). Microperimetry subfield comparison showed significant differences (p&lt;0.0001) in the control group between superior and inferior hemifield as well as between central and peripheral subfields. For eAMD significant differences were found between central and peripheral subfields (p&lt;0.001) and specific subfields (p&lt;0.05) and finally for iAMD between specific quadrants (p&lt;0.05) and specific squares (p&lt;0.05). Significant associations of retinal sensitivity with qCSF metrics were found for the area underneath the logarithmic contrast sensitivity function (AULCSF), contrast acuity (CA) and for the contrast sensitivity at specific spatial frequencies. Conclusions This study showed significant differences in the evaluated retinal sensitivity subfields providing localized natural history data for retinal sensitivity in healthy controls, and patients with eAMD and iAMD.

Left Frontoparietal Control Network Connectivity Moderates the Effect of Amyloid on Cognitive Decline in Preclinical Alzheimer’s Disease: The A4 Study

BackgroundStronger resting-state functional connectivity of the default mode and frontoparietal control networks has been associated with cognitive resilience to Alzheimer’s disease related pathology and neurodegeneration in smaller cohort studies.ObjectivesWe investigated whether these networks are associated with longitudinal CR to AD biomarkers of beta-amyloid (Aβ).DesignLongitudinal mixed.SettingThe Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study and its natural history observation arm, the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study.ParticipantsA sample of 1,021 cognitively unimpaired older adults (mean age = 71.2 years [SD = 4.7 years], 61% women, 42% APOEε4 carriers, 52% Aβ positive).MeasurementsGlobal cognitive performance (Preclinical Alzheimer’s Cognitive Composite) was assessed over an average 5.4 year follow-up period (SD = 2 years). Cortical Aβ and functional connectivity (left and right frontoparietal control and default mode networks) were estimated from fMRI and PET, respectively, at baseline. Covariates included baseline age, APOEε4 carrier status, years of education, adjusted gray matter volume, head motion, study group, cumulative treatment exposure, and cognitive test version.ResultsMixed effects models revealed that functional connectivity of the left frontoparietal control network moderated the negative effect of Aβ on cognitive change (p =.025) such that stronger connectivity was associated with reduced Aβ-related cognitive decline.ConclusionsOur results demonstrate a potential protective effect of functional connectivity in preclinical AD, such that stronger connectivity in this network is associated with slower Aβ-related cognitive decline.

Mapping the evidence about the natural history of acute infections commonly seen in primary care and managed with antibiotics: a scoping review

BackgroundKnowing the natural history of acute infections in primary care, defined as the course of a disease over time in the absence of specific therapy or treatment, can inform clinicians’ and patients’ expectations about illness recovery, but this evidence is fragmented across the literature. This scoping review aimed to map existing research and research gaps relevant to the natural history of acute infections.MethodsWe searched MEDLINE, Embase and CENTRAL using a 2-phase hierarchical search approach. In Phase A, we focused on identifying systematic reviews synthesising natural history data for eligible infections (acute respiratory, urinary, and skin and soft tissue) and systematic reviews of treatment effectiveness (of RCTs with placebo or no treatment arm, or cohort studies). For infections without existing reviews, in Phase B, we searched for primary studies (placebo-controlled RCTs or cohort studies). Two reviewers independently screened and extracted the data (study characteristics, outcome data - e.g., symptom duration, proportion with resolution at various time points).ResultsWe identified 40 systematic reviews, reporting on 45 infections, most commonly (90%) respiratory tract infections. Six (15%) of these aimed to synthesise natural history information. Most reviews reported the proportion of participants with symptom resolution at various time point/s, with 58% providing data on mean symptom duration. Recovery data show the spontaneous resolution of some infections in some people. We found no eligible studies for cellulitis, ecthyma, carbuncle, and erysipelas.ConclusionsOur review has shown that natural history evidence exists for many common acute infections. It can be utilised by clinicians in implementing patient-centred antibiotic stewardship strategies in primary care. Future research should focus on generating natural history evidence for skin and soft tissue infections and urinary tract infections.