Association between lowering restriction levels during the coronavirus outbreak and physical activity among adults: a longitudinal observational study in Brazil

OBJECTIVE The COVID-19 pandemic has had significant consequences on public health and lifestyle and has negatively affected mental health and the level of physical activity worldwide. This study examined the impact of reopening fitness centers and nonessential services and introducing flexible measures to ensure social distancing on physical activity and mental health. MATERIALS AND METHODS This was a longitudinal study. A self-administered questionnaire, including personal, behavioral, physical activity, perception of health, and mood state disorder information, was answered by 128 Brazilians in June 2020 (during severe restrictive measures) and again in April 2021 (after fitness centers and nonessential services were reopened). RESULTS The restriction level adopted in April 2021 was significantly lower than that in June 2020 (p<0.001). The level of physical activity (p<0.001) and health status perception (p<0.001) decreased from June 2020 to April 2021. The median values for depression and anxiety did not differ across the study period. CONCLUSIONS The level of physical activity was reduced during the COVID-19 pandemic, and anxiety and depression were not improved following less restrictive social distancing measures and the reopening of fitness centers. Thus, the return to a prepandemic level of physical activity and mental health status may not be automatic. The results presented herein suggest that the decrease in physical activity observed in the population may be challenging in the postpandemic period

Impact of fecal microbiota transplantation on gut bacterial bile acid metabolism in humans

Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients in which we found that FMT enhanced gut bacterial bile acid metabolism and delayed the development of impaired glucose tolerance relative to the placebo control group. Therefore, we conducted a secondary analysis of fecal samples collected from these patients to assess the potential gut microbial species contributing to the effect of FMT to improve metabolic health and increase gut bacterial bile acid metabolism. Fecal samples collected at baseline and after 4 weeks of FMT or placebo treatment underwent shotgun metagenomic analysis. Ultra-high-performance liquid chromatography-mass spectrometry was used to profile fecal bile acids. FMT-enriched bacteria that have been implicated in gut bile acid metabolism included Desulfovibrio fairfieldensis and Clostridium hylemonae. To identify candidate bacteria involved in gut microbial bile acid metabolism, we assessed correlations between bacterial species abundance and bile acid profile, with a focus on bile acid products of gut bacterial metabolism. Bacteroides ovatus and Phocaeicola dorei were positively correlated with unconjugated bile acids. Bifidobacterium adolescentis, Collinsella aerofaciens, and Faecalibacterium prausnitzii were positively correlated with secondary bile acids. Together, these data identify several candidate bacteria that may contribute to the metabolic benefits of FMT and gut bacterial bile acid metabolism that requires further functional validation

Public health messaging during extreme smoke events: are we hitting the mark?

Background: Emergency services working to protect communities from harm duringwildfires aim to provide regular public advisories on the hazards from fire and smoke.However, there are few studies evaluating the success of public health communicationsregarding the management of smoke exposure. We explored the responses tosmoke-related health advisories of people living in a severely smoke-affected regionduring extensive wildfires in Tasmania, Australia early in 2019. We also evaluatedthe acceptability of portable high efficiency particle air (HEPA) cleaners used in studyparticipant’s homes during the smoky period.Methods: We conducted semi-structured interviews with 24 households in the HuonValley region of Tasmania following a severe smoke episode. These households wereinitially recruited into a HEPA cleaner study. Interviews were recorded, transcribed, andanalyzed for common themes using an inductive framework approach.Results: Public health messaging during the 2019 wildfire event in Tasmania waswidely shared and understood, with social media playing a central role. However,some participants expressed concerns about the timeliness and effectiveness ofthe recommended interventions, and some would have appreciated more detailedinformation about the health risks from smoke. Public messages and actions to protecthouseholds from wildfire threat were, at times, contradictory or dominated in coverageover the smoke messaging, and many participants were conflicted with the multiplepublic messages and action relating to the more serious perceived threat from the fire.Conclusions: Public messaging about smoke and health should continue to usemultiple avenues of communication, with a focus on simple messages provided throughsocial media. Messaging about the smoke hazard should be available from a trustedcentral source regarding all aspects of the wildfire emergency, with links to more detailedinformation including local air quality data alongside interpretation of the associatedhealth risks

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

Structural basis of nuclear import of flap endonuclease 1 (FEN1)

Flap endonuclease 1 (FEN1) is a member of the nuclease family and is structurally conserved from bacteriophages to humans. This protein is involved in multiple DNA-processing pathways, including Okazaki fragment maturation, stalled replication-fork rescue, telomere maintenance, long-patch base-excision repair and apoptotic DNA fragmentation. FEN1 has three functional motifs that are responsible for its nuclease, PCNA-interaction and nuclear localization activities, respectively. It has been shown that the C-terminal nuclear localization sequence (NLS) facilitates nuclear localization of the enzyme during the S phase of the cell cycle and in response to DNA damage. To determine the structural basis of the recognition of FEN1 by the nuclear import receptor importin alpha, the crystal structure of the complex of importin alpha with a peptide corresponding to the FEN1 NLS was solved. Structural studies confirmed the binding of the FEN1 NLS as a classical bipartite NLS; however, in contrast to the previously proposed (KRKX8KKK367)-K-354 sequence, it is the (354)KRX(10)KKAK(369) sequence that binds to importin alpha. This result explains the incomplete inhibition of localization that was observed on mutating residues (KKK367)-K-365. Acidic and polar residues in the X-10 linker region close to the basic clusters play an important role in binding to importin alpha. These results suggest that the basic residues in the N-terminal basic cluster of bipartite NLSs may play roles that are more critical than those of the many basic residues in the C-terminal basic cluster

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Autosomal recessive mutations in nuclear transport factor KPNA7 are associated with infantile spasms and cerebellar malformation

Nuclear import receptors of the KPNA family recognize the nuclear localization signal in proteins and together with importin-β mediate translocation into the nucleus. Accordingly, KPNA family members have a highly conserved architecture with domains that contact the nuclear localization signal and bind to importin-β. Here, we describe autosomal recessive mutations in KPNA7 found by whole exome sequencing in a sibling pair with severe developmental disability, infantile spasms, subsequent intractable epilepsy consistent with Lennox–Gastaut syndrome, partial agenesis of the corpus callosum, and cerebellar vermis hypoplasia. The mutations mapped to exon 7 in KPNA7 result in two amino-acid substitutions, Pro339Ala and Glu344Gln. On the basis of the crystal structure of the paralog KPNA2 bound to a bipartite nuclear localization signal from the retinoblastoma protein, the amino-acid substitutions in the affected subjects were predicted to occur within the seventh armadillo repeat that forms one of the two nuclear localization signal-binding sites in KPNA family members. Glu344 is conserved in all seven KPNA proteins, and we found that the Glu354Gln mutation in KPNA2 is sufficient to reduce binding to the retinoblastoma nuclear localization signal to approximately one-half that of wild-type protein. Our data show that compound heterozygous mutations in KPNA7 are associated with a human neurodevelopmental disease, and provide the first example of a human disease associated with mutation of a nuclear transport receptor

Adductor Myocutaneous Flap Coverage for Hip and Pelvic Disarticulations of Sarcomas with Buttock Contamination

Background: Hip disarticulation and hemipelvectomy are alternatives to limb-salvage procedures for patients with extensive tumors of the upper thigh and buttocks. In cases when neither the conventional posterior gluteus maximus flap nor the anterior quadriceps flap can be used because of the location of the tumor, a medial adductor myocutaneous flap may be an alternative. Description of Technique: The flap is outlined over the anteromedial thigh. The distal extent is at the level of the adductor hiatus. The common femoral vessels and nerve are traced, preserved, and protected. The adductor muscles then are divided above their insertions on the femur and preserved with the flap. En bloc removal of the tumor is performed by either hip disarticulation or hemipelvectomy. The long adductor myocutaneous flap is brought up laterally and proximally to close the wound. Patients and Methods: We reviewed four patients who underwent a medial adductor myocutaneous flap after either hip disarticulation or hemipelvectomy. The medical records and radiographs were analyzed. These patients were followed up for at least a year or until death. Results: Wide surgical margins were achieved in all four patients and the flap remained viable, with no skin necrosis or flap breakdown. The patients were able to sit on the flap, and one patient was able to wear a prosthesis. Conclusions: In patients undergoing hip disarticulation or hemipelvectomy where tumor infiltration or inadvertent contamination by previous surgery will not allow the traditional posterior gluteus maximus or anterior quadriceps flap, this unconventional medial adductor myocutaneous flap is a feasible, technically simple option. Level of Evidence: Level IV therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. © 2010 The Association of Bone and Joint Surgeons®

Epistemic Church's Thesis and absolute undecidability

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