Evolutionary adaptations in the flexor digitorum profundus muscle in Tamandua mexicana (Xenarthra,Myrmecophagidae)

The northern tamandua (Tamandua mexicana) is a neotropical mammal of the order Pilosa, suborder Vermilingua, and family Myrmecophagidae. This species has anatomical and functional adaptations in its forelimb for semiarboreal quadrupedal locomotion. Several studies have reported that the medial head of the triceps brachii and flexor digitorum profundus muscles are fused in species belonging to the family Myrmecophagidae. However, there is no reference to the innervation in these. The triceps brachii muscle is commonly innervated by the radial nerve and the flexor digitorum profundus muscle by the ulnar and median nerves. This study aims to describe the gross anatomy of the flexor digitorum profundus muscle in Tamandua mexicana with respect to the shape, origin, insertion, innervation, and arterial supply. Both forelimbs of nine specimens were used, which were dissected from superficial to deep layers. The formalin-fixed caudomedial forearm muscles were weighed, and the weight percentages of individual forearm muscle specimens were calculated. The flexor digitorum profundus had the highest weight among the forearm muscles and consisted of five heads (three humerals, one radial, and one ulnar). These heads were innervated by median and ulnar nerves; therefore, based on the innervation pattern, we concluded that the medial head of the triceps brachii muscle is not fused with the flexor digitorum profundus. Therefore, the flexor digitorum profundus muscle is highly developed in Tamandua and occupies the caudal part of the arm and forearm, which is an evolutionary adaptation that could have occurred during evolution from the common ancestor of Tamandua and Myrmecophaga.     

Central role of protein kinase Cepsilon in constitutive activation of ERK1/2 and Rac1 in the malignant cells of hairy cell leukemia

We have previously identified the presence of Ras/Raf-independent constitutive activation of extracellular signal-regulated kinase (ERK) in the hairy cells (HCs) of hairy cell leukemia. The aim of the present study was to characterize the signaling components involved in this activation and their relationship to the reported activation of Rac1. We found that both Rac1 and ERK activation in HCs are downstream of active Src and protein kinase C (PKC). Inhibition with toxin B showed that Rac1 plays no role in ERK activation in HCs. However, toxin B inhibited p60src and the Rac1-GEF Vav, demonstrating a positive feedback/activation of p60src by Rac1. Treatment with specific small interfering RNA for various PKC isoforms, or with PKC isoform-specific inhibitors, demonstrated a central role for PKCepsilon in the constitutive activation of Rac1 and ERK in HCs. PKCepsilon and active ERK were mutually associated and co-localized with mitochondria in HCs. Furthermore, active PKCepsilon was nitrated on tyrosine, pointing to a reactive oxygen species-dependent mechanism of activation. By being involved in activation of ERK and Rac1, PKCepsilon plays roles in both the survival of HCs and in the cytoskeletal dynamics responsible for the distinctive morphology and tissue homing of these cells. Our study therefore describes novel aspects of signaling important for the pathogenesis of hairy cell leukemia.     

COVID‐19 lockdown consequences on body mass index and perceived fragility related to physical activity: A worldwide cohort study

BackgroundThis paper is a follow‐up study continuing the COVISTRESS network previous research regarding health‐related determinants.ObjectiveThe aim was to identify the main consequences of COVID‐19 lockdown on Body Mass Index and Perceived Fragility, related to Physical Activity (PA), for different categories of populations, worldwide.DesignThe study design included an online survey, during the first wave of COVID‐19 lockdown, across different world regions.Setting and participantsThe research was carried out on 10 121 participants from 67 countries. The recruitment of participants was achieved using snowball sampling techniques via social networks, with no exclusion criteria other than social media access.Main outcome measures Body Mass Index, Physical Activity, Perceived Fragility and risk of getting infected items were analysed. SPSS software, v20, was used. Significance was set at P < .05.Results Body Mass Index significantly increased during lockdown. For youth and young adults (18‐35 years), PA decreased by 31.25%, for adults (36‐65 years) by 26.05% and for the elderly (over 65 years) by 30.27%. There was a high level of Perceived Fragility and risk of getting infected for female participants and the elderly. Correlations between BMI, Perceived Fragility and PA were identified.Discussion and ConclusionsThe research results extend and confirm evidence that the elderly are more likely to be at risk, by experiencing weight gain, physical inactivity and enhanced Perceived Fragility. As a consequence, populations need to counteract the constraints imposed by the lockdown by being physically active.     

The Pyhäjärvi Cataract Study. I. Study design,baseline characteristics and the demand for cataract surgery

Purpose: The Pyhäjärvi Cataract Study aims to study demand for cataract surgery in the population of a rural town in Finland. Methods: A random, population‐based sample of 881 persons aged ≥ 60 years were interviewed by telephone to obtain a Visual Function‐14 (VF‐14) score. A total of 294 persons were invited for an ophthalmic examination based on three categories of VF‐14 score. Of these, 230 (78%) responded, 10 of whom were excluded as a result of prior bilateral surgery. The New Zealand Priority Criteria (NZPC) and the 15‐Dimension Quality of Life (15‐D) instruments were administered. In addition, another group of 96 patients waiting for cataract surgery were examined and scored using the VF‐14, NZPC and 15‐D instruments. A modified Lens Opacities Classification System (LOCS) III classification was used for grading the cataract. Results: Only one (0.5%) of the 220 examined subjects was referred for cataract surgery. Many patients with relatively good visual acuity (VA), including six people with a 100‐point VF‐14 score suggesting no visual symptoms, were waiting for surgery. Demographic factors were not associated with access to cataract surgery. The patients examined from the waiting list for cataract surgery had more cataractous changes in the lens(es), poorer VA, were older, and scored higher on the NZPC instrument than the population sample examined. Conclusions: Practically no hidden demand for cataract surgery was found in the study population as defined by the national criteria for cataract surgery in Finland. This reflects the fact that the current Finnish health care system appears to recognize and treat cataract patients very well, even in rural areas. Although VA tests may not be sufficient for evaluating need for cataract surgery, the role of questionnaires is not clear either.     

Use of simvastatin treatment in patients with combined hyperlipidemia in clinical practice. For the Simvastatin Combined Hyperlipidemia Registry Group

OBJECTIVE: To describe and understand current care of simvastatin-treated patients with combined hyperlipidemia in routine clinical practice. DESIGN: A 6-month prospective observational study. Demographics, simvastatin dosage, cardiac risk factors, and lipid profile were collected from August 1997 to December 1998 at 20 sites (230 patients) across the United States. RESULTS: Overall mean percentage of reduction in total cholesterol levels was 27% (P<.001), low-density lipoprotein cholesterol (LDL-C) was 35% (P<.001), and triglyceride values was 28% (P<.001). Among those patients with low baseline high-density lipoprotein cholesterol (HDL-C) values (<0.91 mmol/L [<35 mg/dL]) (N = 49), there was a 17% increase in HDL-C (P< or =.001); 35% of these patients achieved National Cholesterol Education Program HDL-C goal (ie, < or =0.91 mmol/L [> or =35 mg/dL]). Coronary heart disease (CHD) patients were given significantly higher initial doses (mean, 15.1 mg) compared with non-CHD patients (mean, 11.5 mg) (P< or =.001). Overall, 74% of patients achieved LDL-C goal (52% on starting dose, 22% after 1 titration). Among those patients who were not at goal and had a follow-up lipid profile result available, only 1 patient (2%) was at the maximum dose (80 mg); 69% were receiving 20 mg or less. Approximately 63% of patients with CHD, 80% of patients with 2 or more risk factors, and 91% of patients with fewer than 2 risk factors achieved LDL-C goal. CONCLUSIONS: Multiple factors contribute to LDL-C goal achievement in a usual care setting. A significant opportunity exists to increase the number of patients who achieve LDL-C goal by appropriate dose titration and/or give patients a higher initial dose of simvastatin.     

Modulatory effects of melatonin on behavior, hemolymph metabolites, and neurotransmitter release in crayfish

Melatonin affects a variety of circadian processes such as behavior and neurotransmitter release in vertebrates. Crayfish melatonin production occurs in the eyestalks, and the cycle of production may change seasonally. To date, however, melatonin's roles and mechanisms of action in crustacean physiology are unclear. We injected melatonin or saline into crayfish in scotophase and monitored activity and hemolymph glucose/lactate over 24 h in early spring. Crayfish were significantly more active in photophase versus the expected scotophase, and had concurrent glucose/lactate peaks. Melatonin reversed the activity pattern, causing a scotophase activity peak, but not the glucose/lactate patterns. This study was repeated in late summer, during which control activity and glucose/lactate levels were elevated in scotophase. Melatonin decreased the amplitude of scotophase activity and glucose/lactate, eliminating activity and glucose cycles. We also injected melatonin or saline at various times of day in early summer and monitored locomotor activity for 1 h. Controls had high activity at 1200 (mid-photophase) and 2100 h (early scotophase), and melatonin increased activity at 1200 h but decreased it at 2100 h. Melatonin also increased activity at 1500 h but not 1800 h (late photophase). Next, we examined the influence of melatonin on crayfish neurophysiology. Melatonin (10 microM) enhanced synaptic transmission at the neuromuscular junction (NMJ). The presynaptic action resulted in more vesicles being released during evoked stimulation. Our study indicates that melatonin may have a phylogenetically conserved role in the transduction of circadian information in invertebrates as in vertebrates. Behavioral and physiological effects may be mediated by modulation of central pathways, enhanced at the peripheral level via neuromodulation of the NMJ.     

Glycinergic and GABAergic calcium responses in the developing lateral superior olive

The lateral superior olive (LSO), a binaural nucleus involved in sound localization, receives tonotopically organized inhibitory inputs from the medial nucleus of the trapezoid body (MNTB). During development, the tonotopic organization of this glycinergic/GABAergic MNTB-LSO pathway is established by activity-dependent axonal reorganization. However, the underlying mechanisms by which this reorganization takes place have remained largely unknown. As cytosolic calcium is one of the most important second messengers responsible for inducing synaptic plasticity and reorganization, we examined whether and how activity in the MNTB-LSO pathway changes the intracellular calcium concentration ([Ca2+]i) in developing LSO neurons. By applying calcium imaging techniques to Fura-2-labelled slices from neonatal rats and mice, we found that glycine and GABA (gamma-aminobutyric acid) affect [Ca2+]i in LSO neurons in an age-dependent manner; during the first postnatal week, the period at which glycine and GABA are depolarizing in the LSO, glycine and GABA always increased [Ca2+]i. However, in 2-week-old animals, the time around hearing onset when glycine and GABA are hyperpolarizing, glycine and GABA slightly decreased [Ca2+]i. Calcium responses could also be elicited by stimulation of afferent fibres from the MNTB, and these synaptic responses were mediated by glycine and GABA(A) receptors. Furthermore, GABA, which is a neurotransmitter only in the immature MNTB-LSO pathway, played a major role in generating MNTB-elicited Ca2+ responses. The direct link of glycinergic/GABAergic synaptic activity to intracellular calcium signalling during the period of inhibitory synaptic plasticity could be one of the mechanisms by which tonotopic MNTB-LSO connections become established.     

Rate of migration of oral leukocytes in patients with periodontitis.

The rate of migration of leukocytes (OMR) was estimated by counts of sequential mouthrinses in 81 human subjects in order to evaluate its usefulness as a laboratory test of oral inflammation. Periodontitis was taken as a model, and neither patients nor controls had any other oral inflammation. Patients with advanced periodontitis, but with periodontal destruction of about the same level, were divided into two groups, acute phase and chronic phase. The mean number of leukocytes entering the oral cavity in 30 s was estimated in these two groups. In the same patients the difference between the cell count in the first rinse and the OMR level was estimated, to test whether it could be taken to indicate the grade of acuteness of the inflammation (GAI). OMR and GAI were assessed in the patients with periodontitis after the initial treatment and at follow-up 1 year after completion of the full treatment, which almost always included surgical procedures. The results indicate that the OMR reflects the existence of oral inflammation and can be used as a laboratory test with the same reservations as white blood cell counts for systemic inflammation. The difference in GAI between patients in the acute and chronic phases of the disease was highly significant, indicating that this test gives information about the severity of the inflammation.