Relevant Clinical Observations Research Articles

Advances in Clinical Research in Chinese Medicine for Decreased Ovarian Reserve Function

Decreased ovarian reserve function (DOR) is a pre-disease state of premature ovarian failure (POF), the pathogenesis of which is not well understood and the disease is insidious, so early detection and active treatment can save adverse outcomes. In recent years, the incidence of DOR has become younger, which seriously affects women's physical and mental health. In this paper, we analyze the etiology and clinical treatment methods from relevant experimental studies and clinical observations in the past 5 years, in order to provide theoretical support and treatment ideas for female reproductive health.

Basal Septal Hypertrophy as the Early Imaging Biomarker for Adaptive Phase of Remodeling Prior to Heart Failure.

Hypertension plays a dominant role in the development of left ventricular (LV) remodeling and heart failure, in addition to being the main risk factor for coronary artery disease. In this review, we focus on the focal geometric and functional tissue aspects of the LV septal base, since basal septal hypertrophy (BSH), as the early imaging biomarker of LV remodeling due to hypertensive heart disease, is detected in cross-sectional clinic studies. In addition, the validation of BSH by animal studies using third generation microimaging and relevant clinical observations are also discussed in the report. Finally, an evaluation of both human and animal quantitative imaging studies and the importance of combined cardiac imaging methods and stress-induction in the separation of adaptive and maladaptive phases of the LV remodeling are pointed out. As a result, BSH, as the early imaging biomarker and quantitative follow-up of functional analysis in hypertension, could possibly contribute to early treatment in a timely fashion in the prevention of hypertensive disease progression to heart failure. A variety of stress stimuli in etiopathogenesis and the difficulty of diagnosing pure hemodynamic overload mediated BSH lead to an absence of the certain prevalence of this particular finding in the population.

An Integrated Platform for Skin Cancer Heterogenous and Multilayered Data Management

Electronic health record (EHR) systems improve health care services by allowing the combination of health data with clinical decision support features and clinical image analyses. This study presents a modular and distributed platform that is able to integrate and accommodate heterogeneous, multidimensional (omics, histological images and clinical) data for the multi-angled portrayal and management of skin cancer patients. The proposed design offers a layered analytical framework as an expansion of current EHR systems, which can integrate high-volume molecular -omics data, imaging data, as well as relevant clinical observations. We present a case study in the field of dermatology, where we attempt to combine the multilayered information for the early detection and characterization of melanoma. The specific architecture aspires to lower the barrier for the introduction of personalized therapeutic approaches, towards precision medicine. The paper describes the technical issues of implementation, along with an initial evaluation of the system and discussion.

Autonomous Systems in Anesthesia: Where Do We Stand in 2020? A Narrative Review.

As most of us are aware, almost every facet of our society is becoming, for better or worse, progressively more technology-dependent. Technological advancement has made autonomous systems, also known as robots, an integral part of our life in several fields, including medicine. The application of robots in anesthesia could be classified into 3 types of robots. The first ones are pharmacological robots. These robots are based on closed-loop systems that allow better-individualized anesthetic drug titration for optimal homeostasis during general anesthesia and sedation. Recent evidence also demonstrates that autonomous systems could control hemodynamic parameters proficiently outperforming manual control in the operating room. The second type of robot is mechanical. They enable automated motorized reproduction of tasks requiring high manual dexterity level. Such robots have been advocated to be more accurate than humans and, thus, could be safer for the patient. The third type is a cognitive robot also known as decision support system. This type of robot is able to recognize crucial clinical situation that requires human intervention. When these events occur, the system notifies the attending clinician, describes relevant related clinical observations, proposes pertinent therapeutic options and, when allowed by the attending clinician, may even administer treatment. It seems that cognitive robots could increase patients' safety. Robots in anesthesia offer not only the possibility to free the attending clinicians from repetitive tasks but can also reduce mental workload allowing them to focus on tasks that require human intelligence such as analytical and clinical approach, lifesaving decision-making capacity, and interpersonal interaction. Nevertheless, further studies have yet to be done to test the combination of these 3 types of robots to maintain simultaneously the homeostasis of multiple biological variables and to test the safety of such combination on a large-scale population.

The Assessment of Upper Limb Functionality in Friedreich Ataxia via Self-Feeding Activity

The objective assessment of motor impairment resulting from neurological disorders forms the basis for effective rehabilitation and therapeutic programs. Such assessments conducted through the engagement of suitable daily activities can serve as an effective surrogate measure for the assessment of independent living. This study considers an instrumented spoon in the assessment of upper-limb functionality through the self-feeding activity of a group of individuals clinically diagnosed with the debilitating condition, Friedreich ataxia (FRDA). Thirty-five subjects with FRDA (34 ± 14 years old) and 14 age-matched healthy subjects performed three cycles of self-feeding consisting of grasping, scooping, transferring food to mouth and returning the spoon. Parameters relating to the feeding rate, trajectory of the rotation, range of motion and movement variability with specific attention to each segment were considered for the capture of ataxia pertaining to the disability. Movement variability measured by Dynamic Time Warping (DTW) resulted in an average accuracy of 96% in the diagnosis of ataxia (separation of the two cohorts). The severity of ataxia estimated using a combination of features from Random Forest (RF) increased the correlation with the clinical estimates of ataxia by 13% and achieved higher coefficient (0.72 in patient scale) than the currently used tests (Box & Block, Pegboard). While the overall results provided an objective, daily activity based means of capturing intrinsic abnormalities, the different segments of the task demonstrated the presence of ataxia in a spatial context concurring with relevant clinical observations.

Photo-toxicité rétinienne et pollution lumineuse : intérêts et apports de l’ophtalmologie vétérinaire

Retinal photo-toxicity & light pollution : interests & contribution of the veterinary ophthalmology Two reports of the French ANSES (Agence Nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail) highlighted the potential risks of exposure to lighting systems using light-emitting diodes (LED), especially because emitting short wavelengths (blue light), on the human, animal and environmental healthes. Two dangers have been identified : the retinal phototoxicity and the biological circadian rythms deregulation (chrono-disruption). Acute exposure to intense light induces retinal cell death that can lead to blindness. Chronic exposure to low-intensity phototoxic light accelerates the aging process of retinal tissues, that can lead to degenerative diseases such as Age-related Macular Degeneration (AMD). The authors of these reports considered that it would be appropriate to evaluate the extrapolation to humans of the results obtained in laboratory animals. The purpose of this article is to illustrate the contribution that veterinary ophthalmology could provide through relevant clinical observations in companion animals, considered as animal-patients, and in livestock collectively subjected to artificial light creating bright environments imposed by farming practices, considered to be – because of their large numbers – environmental sentinels. The deleterious effects of light are summarized in a section devoted to the laboratory animal and then the main methods of clinical diagnosis of retinal dysfunction, common to human and veterinary ophthalmology, are described. Obviously, the concept of uniqueness of health (One health, One medicine) applies to this problem of light pollution : human and veterinary medicine must work together for a systemic appreciation of human-animal-environment relationships.

Pathogenesis of ANCA-Associated Pulmonary Vasculitis.

Antineutrophil cytoplasmic antibodies (ANCAs) are autoantibodies specific for antigens located in the cytoplasmic granules of neutrophils and lysosomes of monocytes. ANCAs are associated with a spectrum of necrotizing vasculitis that includes granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis. Pulmonary vasculitis and related extravascular inflammation and fibrosis are frequent components of ANCA vasculitis. In this review, we detail the factors that have been associated with the origin of the ANCA autoimmune response and summarize the most relevant clinical observations, in vitro evidence, and animal studies strongly indicating the pathogenic potential of ANCA. In addition, we describe the putative sequence of pathogenic mechanisms driven by ANCA-induced activation of neutrophils that result in small vessel necrotizing vasculitis and extravascular granulomatous necrotizing inflammation.

Leydig cell insufficiency in hypospermatogenesis: a paracrine effect of activin-inhibin signaling?

Clinical findings and a variety of experimental models indicate that Leydig cell dysfunction accompanies damage to the seminiferous tubules with increasing severity. Most studies support the idea that intratesticular signaling from the seminiferous tubules to Leydig cells regulates steroidogenesis, which is disrupted when hypospermatogenesis occurs. Sertoli cells seem to play a pivotal role in this process. In this review, we summarize relevant clinical and experimental observations and present evidence to support the hypothesis that testicular activin signaling and its regulation by testicular inhibin may link seminiferous tubular dysfunction to reduced testosterone biosynthesis.

Toward a model of continuous care: A necessity for caregiving partners.

Caregiving partners constitute a unique group, who provide both physical and emotional care for patients. There has been extensive research conducted on caregivers during either the caregiving or bereavement phase; however, these phases are often treated as separate entities rather than as part of a continuum. In this paper, utilizing relevant literature and clinical observations, we map the emotional journey and lived experience of caregivers moving from disease progression, to the end of life, to the dying process itself, and then through life after the death of a partner. Along this journey, we identify the links between pre-death caregiving and bereavement. Our illustration raises awareness regarding the unmet needs experienced by caregiving partners across the continuum and provides an alternative framework through which clinicians can view this course. of Results We bolster arguments for improved palliative care services and early interventions with distressed caregiving partners by emphasizing continuity of care both before and after a patient's death.

Modifying the Rizzoli foot model to improve the diagnosis of pes-planus: application to kinematics of feet in teenagers.

BackgroundA number of multi-segment foot protocols have been proposed to obtain measurements of clinical value. In the clinical assessment of foot pathologies and deformities, such as in the pes-planus, the frontal-plane alignment of the calcaneus and the dynamic properties of the medial longitudinal arch are critical parameters though often neglected by the majority of foot protocols. The aim of the present work is to modify an established foot protocol to obtain static and kinematic measures more consistent with corresponding clinical observations. Moreover, while many papers have reported kinematic data from varying populations, few investigations have focussed on young participants from same-age cohorts.MethodsA 6-camera motion capture system was employed to track the shank, rear-, mid- and fore-foot segments in the left and right leg of 10 children (13.1 ± 0.8 years) during gait. Three markers were attached to each segment thus allowing for triplanar motion of five joints to be described according to the Rizzoli Foot Model. An additional marker was attached to the posterior bottom of the calcaneus to enhance measurement of frontal-plane orientation. Description of the medial longitudinal arch angle was redefined to be more consistent with rearfoot orientation and to common clinical assessments. A novel 3-marker description of the hallux segment was implemented to improve robustness in calculating 1st metatarso-phalangeal joint rotations.ResultsFoot segments kinematics showed good inter- participant repeatability and overall consistency with previous similar reports. 15 out of 20 feet showed neutral or slightly valgus orientation of the calcaneus. Relatively large medial longitudinal arch angles (mean 186 ± 16 deg) were found in the present young population. Both measurements were reasonably in accordance with the relevant clinical observations of these feet.ConclusionsModifications to a widely used multisegmental foot kinematic model were implemented to improve robustness and consistency with relevant clinical observations. A detailed description of foot joints motion during barefoot walking in a population of 13-year old children with apparent flat feet has been presented, which may provide useful information to investigate the development of gait in children and the diagnosis of flexible flat foot.

Cervical mucus from biochemical structure to clinical implications

Structure of human cervical mucus plays a pivotal role in female fertility and protection of reproductive health. Investigation of biochemical and biophysical structure of cervical mucus remains a challenge due to complex structural proteins, high content of oligosaccharides and cyclic variability of its structure. We present the current knowledge on chemical and biophysical features of cervical mucus and regulation of its secretion, relevant clinical observations and underexplored elements. The latter relates to biochemical background of physical properties and antimicrobial activity of cervical mucus, and regulation of its production.

Morgellons Disease: A Chemical and Light Microscopic Study

Morgellons disease is an emerging multisystem illness characterized by unexplained dermopathy and unusual skin- associated filament production. Despite evidence demonstrating that an infectious process is involved and that lesions are not self-inflicted, many medical practitioners continue to claim that this illness is delusional. We present relevant clinical observations combined with chemical and light microscopic studies of material collected from three patients with Morgellons disease. Our study demonstrates that Morgellons disease is not delusional and that skin lesions with unusual fibers are not self-inflicted or psychogenic. We provide chemical, light microscopic and immunohistological evidence that filaments associated with this condition originate from human epithelial cells, supporting the hypothesis that the fibers are composed of keratin and are products of keratinocytes.

The Aging of Anna Freud’s Diagnostic Profile

In 1962 Anna Freud published her pioneering paper on the Diagnostic Profile, proposing a framework for organizing relevant clinical material and observations for the assessment of a child's inner world. Since that time, the Profile has been applied, with modifications, to work with babies, adolescents, adults, blind children, and others. This paper strives to demonstrate the Profile's applicability to a group often neglected in the psychoanalytic literature, namely the older population, a vibrant group frequently seeking psychotherapy and even psychoanalysis. A case study of a woman in her 70s is used to illustrate the advantages for clinicians of the Profile for a clearer understanding, both diagnostically and intrapsychically, of the older adult.

How do microclimate factors affect the risk for superficial pressure ulcers: A mathematical modeling study

In this study, a mathematical model is developed for analyzing the effects of the microclimate on skin tolerance to superficial pressure ulcers (SPUs). The modeling identified the following factors as such that decrease the tolerance of skin to SPUs: (i) increase in the skin temperature, (ii) increase in the ambient temperature, (iii) increase in the relative humidity, (iv) increase in the skin–support (or skin–clothing–support) contact pressures, and (v) decrease in permeabilities of the materials contacting the skin or being close to it, e.g. the covering sheet of the support and clothing. The modeling is consistent with relevant empirical findings and clinical observations documented in the literature, explains them from a basic science aspect, and can be further developed for design of interventions, safer patient clothing and supports that consider the optimization of microclimate factors.

Urinary parameters predictive of cisplatin-induced acute renal injury in dogs

A 28-day study was conducted to evaluate changes in urinary cytokine/chemokine expression levels in dogs with renal injury due to administration of cisplatin. Animals ( n = 17) were administered cisplatin at 0.75 mg/kg/day (i.v.) for five consecutive days. Urine/serum were collected at pre-dosing, 4 h post-dosing and on days 2, 3, 4, 8, 10, 14, 16, 18, 21, 23, 25, 28 and unscheduled terminations. Animals were euthanized when serum creatinine (sCr) levels measured at ⩾1.9 mg/dL, indicating significant loss of renal function (decreased glomerular filtration rate). Relevant clinical observations included lethargy and dehydration. Pre-study sCr levels ranged from 0.6 to 0.8 mg/dL; on days 1 through 4, sCr levels ranged from 0.5 and 1.1 mg/dL; and terminal sCr levels ranged from 0.6 and 6.6 mg/dL. Histologically, cisplatin-related renal changes were characterized as proximal tubule dilatation, vacuolization, degeneration, regeneration, and interstitial inflammation. Increased interleukin (IL)-2, IL-8, monocyte chemoattractant protein-1 (MCP-1), granulocyte–macrophage colony-stimulating factor (GMCSF) and keratinocyte-derived chemokine (KC) occurred on days 3 through 4. Increased IL-7 occurred on day 4. This study showed for the first time that inflammatory cytokines/chemokines in urine positively identified acute renal tubular injury in dogs at time points earlier than sCr, a traditional marker of nephrotoxicity.

Safety of an amino-acetonitrile derivative (AAD), monepantel, in ewes and their offspring following repeated oral administration

AIM: To demonstrate the clinical and reproductive safety in ewes and their offspring of repetitive oral doses of monepantel, an amino-acetonitrile derivative (AAD), when administered at three times the proposed maximum recommended dose (MRD) over an entire reproductive cycle. METHODS: A randomised controlled blinded study design was used. One hundred and twelve primi- or multi-parous ewes and 28 rams were randomly allocated into control and treated groups (n=56 for groups of ewes, n=14 for groups of rams). Two control ewes and two treated ewes were randomly selected to form 28 subgroups. A control or treated ram was then randomly allocated to each subgroup, to form control ram/treated ewe, control ram/control ewe, treated ram/treated ewe, and treated ram/control ewe ‘treatment/mating’ units. Control animals were treated with saline, and treated animals given three times the MRD (11.25 mg/kg) of monepantel. Treatments were administered orally every 5 days during an entire reproductive cycle, including oestrus and mating, gestation, and post-lambing to weaning. Detailed recording at multiple time points were made of veterinary examinations; observations for adverse events; bodyweight measurements; faecal scores; and haematology, clinical chemistry and coagulation variables. Reproductive indices determined included percent pregnant, number of failed embryos, abortion percentage, number of lambs with teratogenic defects, length of gestation, percentage of stillbirths, number of ewes experiencing reproductive problems, lambing percentage, and pre-weaning mortality. Post-mortem examination, including measurement of organ weights, was performed on randomly selected ewes (n=40) and lambs (n=40) at the completion of the study. RESULTS: All ewes treated with monepantel and those in the control group thrived and behaved normally to the end of the study. No treatment-related, toxicologically relevant adverse events, clinical observations or gross post-mortem changes were observed. Furthermore, there were no significant differences in bodyweight or organ weights, and haematological, clinical chemistry or coagulation variables between ewes treated with monepantel and control ewes. No significant differences were observed in any of the reproductive indices measured. No significant clinical differences were noted between lambs born from treated ewes and those from controls. CONCLUSIONS AND CLINICAL RELEVANCE: Repeated oral administration of monepantel at three times the MRD every 5 days over an entire reproductive cycle was not associated with any treatment-related adverse effects on the reproductive performance of ewes nor on the viability of their offspring, and was systemically very well tolerated. This study demonstrated that this population of ewes could tolerate accidental overdoses of up to three times the MRD of monepantel or prolonged repetitive administration of overdoses. Thus, those so treated entering a breeding programme would have normal reproductive indices, mating behaviour, and health, and their lambs would suffer no ill effects.

Reproductive safety of an amino-acetonitrile derivative (AAD), monepantel, in rams following repeated oral administration

AIM: To demonstrate the clinical and reproductive safety in rams of repetitive oral doses of monepantel, an amino-acetonitrile derivative (AAD), when administered at three times the proposed maximum recommended dose (MRD) over an entire spermatogenic cycle and during mating with ewes. METHODS: A randomised controlled blinded study design was used with 28 rams randomly divided into two groups. The control group was treated with saline, and the other group was given three times the MRD (11.25 mg/kg) of monepantel. Treatments were administered orally every 5 days, for 100 days, during an entire spermatogenic cycle and subsequent mating period. Detailed recording at multiple time points were made of veterinary examinations; observations for adverse events; bodyweight measurements; faecal scores; haematology, clinical chemistry and coagulation variables; semen indices; evaluation of serving capacity; and gross pathology (including measurement of organ weights) performed on 10 rams from each group at the completion of the study. RESULTS: All rams treated with monepantel and those in the control group thrived and behaved normally to the end of the study. No treatment-related, toxicologically relevant adverse events, clinical observations or macroscopic changes were observed. Furthermore, there were no significant differences in bodyweight or organ weights, and haematological, clinical chemistry or coagulation variables between rams treated with monepantel and control rams. No significant changes were observed in any semen variable measured in any rams, and the serving capacity of rams mated to ewes was unaffected. CONCLUSIONS AND CLINICAL RELEVANCE: Repeated oral administration of monepantel at three times the MRD every 5 days over an entire spermatogenic cycle and during mating was not associated with any treatment-related adverse effects on the reproductive performance of rams and was systemically very well tolerated. This study demonstrated that this population of rams could tolerate accidental overdoses of up to three times the MRD of monepantel or prolonged repetitive administration at overdoses. Thus, those so treated entering a breeding programme would have normal sperm indices, mating behaviour, and health.

Safety of an amino-acetonitrile derivative (AAD), monepantel, in weaned lambs following repeated oral administration

AIM: To demonstrate the safety in weaned lambs of repetitive oral doses of monepantel, an amino-acetonitrile derivative (AAD), when administered at the proposed maximum recommended dose (MRD) and three and five times the MRD over 24 weeks. METHODS: A randomised controlled blinded study design was used. Fifty-six weaned lambs were randomly allocated into a control group, the MRD (3.75 mg/kg) and three (11.25 mg/ kg) and five (18.75 mg/kg) times the MRD treatment groups (n=7 castrated males plus seven females each). Treatment doses of monepantel were calculated based on the MRD of 3.75 mg/ kg, and administered orally on eight occasions at intervals of approximately 21 days. Detailed recording at multiple time points were made of veterinary examinations, observations for adverse events, bodyweight measurements, faecal scores, and haematology, clinical chemistry and coagulation variables. Gross pathology (including measurement of organ weights) and histopathology were performed at the completion of the study. RESULTS: All lambs treated with monepantel and those in the control group thrived, grew and behaved normally to the end of the study. No treatment-related, toxicologically relevant adverse events, clinical observations or macroscopic or microscopic changes were observed. Furthermore, there were no significant differences in bodyweight or organ weights, and haematological, clinical chemistry or coagulation variables between lambs treated with monepantel and control lambs. CONCLUSIONS AND CLINICAL RELEVANCE: Repeated oral administration of monepantel at the MRD and three and five times the MRD every 3 weeks for eight treatments was not associated with any treatment-related adverse effects and was systemically very well tolerated in weaned, growing lambs. This study demonstrated that this population of lambs could tolerate accidental overdoses of up to five times the MRD of monepantel or prolonged repetitive administration at recommended doses or overdoses.

Some Dynamic Aspects of Hematopoietic Stem Cells

Hematopoiesis is the process responsible for maintaining the number of circulating blood cells that are undergoing continuous turnover. At the root of this process are the hematopoietic stem cells (HSC). In the following we discuss various dynamic aspects of HSC behavior ranging from the number of active stem cells, their expansion during ontogeny and the importance of stochastic effects on their behavior. We show how mathematical modeling of HSC behavior can provide important insights on these cells and clarify the implications of these dynamical aspects on healthy and sick individuals, as such providing rational explanations for relevant clinical observations on disorders that originate in this group of cells.

A procedure‐specific systematic review and consensus recommendations for analgesia after total hip replacement

Total hip replacement is a major surgical procedure usually associated with significant pain in the early postoperative period. Several anaesthetic and analgesic techniques are in common clinical use for this procedure but, to date, clinical studies of pain after total hip replacement have not been systematically assessed. Using the Cochrane protocol, we have conducted a systematic review of analgesic, anaesthetic and surgical interventions affecting postoperative pain after total hip replacement. In addition to the review, transferable evidence from other relevant procedures and clinical practice observations collated by the Delphi method were used to develop evidence-based recommendations for the treatment of postoperative pain. For primary total hip replacement, PROSPECT recommends either general anaesthesia combined with a peripheral nerve block that is continued after surgery or an intrathecal (spinal) injection of local anaesthetic and opioid. The primary analgesic technique should be combined with a step-down approach using paracetamol plus conventional non-steroidal anti-inflammatory drugs, with strong or weak opioids as required.