Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression

Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. Methods: This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. Results: The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale. Secondary outcomes include functioning, substance use, mania ratings, and quality of life. Blood samples will be collected at baseline and week 16 to explore biochemical alterations following treatment. Conclusion: This study may provide a novel adjunctive treatment for bipolar depression. Analysis of biological samples may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression

Kesesuaian Langkah Memperkasakan Domain Bandar Berdaya Huni di Zon Black Spot Jenayah di Sabah

Persoalan pangkal terhadap penyelesaian konflik ruangan perlu dilaksanakan segera antaranya untuk mewujudkan sebuah ruangan bandar yang berdaya huni untuk komuniti. Bagi mencapai matlamat keruangan tersebut, penekanan perlu diambil perhatian terhadap aspek keselamatan, keselesaan dan kesejahteraan ruangan fizikal. Justeru, dalam menyediakan ruangan fizikal seimbang, penelitian pemerkasaan berfokuskan kepada tiga domain bandar berdaya huni perlu dilakukan iaitu domain perumahan, domain ruang awam dan bangunan dan domain pengangkutan dan jalan raya. Makalah ini menjelaskan kesesuaian langkah memperkasakan domain bandar berdaya huni di zon black spot jenayah di Sabah merangkumi lima belas (15) zon black spot jenayah di sekitar Kota Kinabalu, Sandakan dan Tawau. Soal selidik diedarkan kepada 1,152 responden dan data dianalisis melalui SPSS menggunakan kaedah skor min. Penemuan mendapati langkah sesuai yang menjadi pilihan dominan responden bagi domain perumahan adalah melaksanakan aktiviti rondaan dan kawalan keselamatan tidak kira siang atau malam di kawasan perumahan (4.59). Manakala, domain ruang awam dan bangunan pula dengan memastikan pengurusan sisa pepejal adalah sistematik dengan nilai skor min (4.57). Sementara itu, domain pengangkutan dan jalan raya menekankan kekerapan menyelenggarakan jalan raya untuk kegunaan komuniti (4.62). Walau bagaimanapun, hasil analisis mengikut zon adalah berbeza mengikut ruangan dan lokasi. Oleh itu, adalah perlu pihak berwajib mengambil kira dan meneliti maklum balas komuniti dalam ruangan dalam memastikan usaha memperkasakan ruangan bandar berjalan baik

Chimpanzees make tactical use of high elevation in territorial contexts

Tactical warfare is considered a driver of the evolution of human cognition. One such tactic, considered unique to humans, is collective use of high elevation in territorial conflicts. This enables early detection of rivals and low-risk maneuvers, based on information gathered. Whether other animals use such tactics is unknown. With a unique dataset of 3 years of simultaneous behavioral and ranging data on 2 neighboring groups of western chimpanzees, from the Taï National Park, Côte d’Ivoire, we tested whether chimpanzees make decisions consistent with tactical use of topography to gain an advantage over rivals. We show that chimpanzees are more likely to use high hills when traveling to, rather than away from, the border where conflict typically takes place. Once on border hills, chimpanzees favor activities that facilitate information gathering about rivals. Upon leaving hills, movement decisions conformed with lowest risk engagement, indicating that higher elevation facilitates the detection of rivals presence or absence. Our results support the idea that elevation use facilitated rival information gathering and appropriate tactical maneuvers. Landscape use during territorial maneuvers in natural contexts suggests chimpanzees seek otherwise inaccessible information to adjust their behavior and points to the use of sophisticated cognitive abilities, commensurate with selection for cognition in species where individuals gain benefits from coordinated territorial defense. We advocate territorial contexts as a key paradigm for unpicking complex animal cognition

Domain formation in DODAB–cholesterol mixed systems monitored via nile red anisotropy

The effect of the cholesterol (Ch) on liposomes composed of the cationic lipid dioctadecyldimethylammonium bromide (DODAB) was assessed by studying both the steady-state and time-resolved fluorescence anisotropy of the dye Nile Red. The information obtained combined with analysis of the steady-state emission and luorescence lifetime of Nile Red (NR) for different cholesterol concentrations (5–50%) elucidated the presence of “condensed complexes” and cholesterol-rich domains in these mixed systems. The steady-state fluorescence spectra were decomposed into the sum of two lognormal emissions, emanating from two different states, and the effect of temperature on the anisotropy decay of Nile Red for different cholesterol concentrations was observed. At room temperature, the time-resolved anisotropy decays are indicative of NR being relatively immobile (manifest by a high r∞ value). At higher temperature, rotational times ca. 1 ns were obtained throughout and a trend in increasing hindrance was seen with increase of Ch content

Postweaning maternal care increases male chimpanzee reproductive success

International audienceHumans are unusual among animals for continuing to provision and care for their offspring until adulthood. This "prolonged dependency" is considered key for the evolution of other notable human traits, such as large brains, complex societies, and extended postreproductive lifespans. Prolonged dependency must therefore have evolved under conditions in which reproductive success is gained with parental investment and diminished with early parental loss. We tested this idea using data from wild chimpanzees, which have similarly extended immature years as humans and prolonged mother-offspring associations. Males who lost their mothers after weaning but before maturity began reproducing later and had lower average reproductive success. Thus, persistent motherimmature son associations seem vital for enhancing male reproductive success, although mothers barely provision sons after weaning. We posit that these associations lead to social gains, crucial for successful reproduction in complex social societies, and offer insights into the evolution of prolonged dependency

Tool use behavior in three wild bonobo communities at Kokolopori

Abstract Comparative studies on tool technologies in extant primates, especially in our closest living relatives, offer a window into the evolutionary foundations of tool use in hominins. Whereas chimpanzee tool technology is well studied across populations, the scarcity of described tool technology in wild populations of our other closest living relative, the bonobo, is a mystery. Here we provide a first report of the tool use repertoire of the Kokolopori bonobos and describe in detail the use of leaf-umbrellas during rainfall, with the aim to improve our knowledge of bonobo tool use capacity in the wild. The tool use repertoire of the Kokolopori bonobos was most similar to that of the nearby population of Wamba and comprised eight behaviors, none in a foraging context. Further, over a 6-month period we documented 44 instances of leaf-umbrella use by 22 individuals from three communities, suggesting that this behavior is habitual. Most leaf-umbrella tool users were adult females, and we observed a nonadult using a leaf-umbrella on only a single occasion. While the study and theory of tool technologies is often based on the use of tools in foraging tasks, tool use in bonobos typically occurs in nonforaging contexts across populations. Therefore, incorporating both foraging and nonforaging contexts into our theoretical framework is essential if we wish to advance our understanding of the evolutionary trajectories of tool technology in humans

USAHA MEMBANGUNKAN MODEL HOMESTAY PATUH SYARIAH (MHPS): MENERAJUI PELANCONGAN ISLAMIK DI SABAH

Sabah, sebagai salah satu negeri di Malaysia yang kaya dengan keindahan alam semula jadi dan kepelbagaian budaya, mempunyai potensi besar untuk menjadi destinasi pelancongan utama dalam konteks pelancongan Islamik. Kajian ini menyelidiki pentingnya usaha membangunkan Model Homestay Patuh Syariah (MHPS) di Sabah dalam menggerakkan industri pelancongan Islamik. MHPS membawa bersama elemen-elemen penting yang merangkumi pematuhan syariah, pemeliharaan budaya tempatan, peluang ekonomi, dan kelestarian alam semula jadi. Pematuhan kepada nilai-nilai syariah Islam di dalam pengurusan homestay akan menarik pelancong Muslim yang mencari pengalaman pelancongan yang sejajar dengan prinsip-prinsip agama mereka. Kajian ini menggunakan data kuantitatif dan kualitatif yang diperolehi melalui kaedah pemerhatian langsung, temubual mendalam, sorotan literatur dan edaran soal selidik sebagai senarai semak. Hasil kajian mendapati, penilaian pemarkahan pematuhan elemen patuh syariah dalam perkhidmatan homestay yang dilawati tidak mencapai (100%) iaitu (89.3%). Markah tertinggi dicatatkan adalah sebanyak 25 dari 28 pematuhan elemen patuh syariah yang diteliti. Justeru, melalui penelitian pengaplikasian ciri-ciri perkhidmatan penginapan patuh syariah yang dilihat relevan dan sesuai untuk diangkat menjadi kateristik dalam Model Homestay Patuh Syariah (MHPS) perlu segera dibangunkan sebagai satu panduan dan rujukan kepada para pengusaha homestay sedia ada. Dengan itu, MHPS bukan sahaja membuka peluang pelancongan yang baru tetapi juga memperluaskan sumber pendapatan dalam industri pelancongan. Selain itu, MHPS akan mencipta peluang pekerjaan untuk penduduk tempatan dalam bidang pengurusan homestay, perkhidmatan pelancongan, dan banyak lagi sekaligus bermanfaat membantu mengatasi isu pengangguran dalam kalangan komuniti tempatan. Seterusnya, dengan membangunkan MHPS juga dapat membantu dalam pemeliharaan warisan budaya Sabah agar tradisi tempatan terus hidup sebagai warisan kepada generasi akan datang. Kelestarian alam semula jadi juga menjadi keutamaan dalam pengurusan homestay, memastikan keindahan alam dikekalkan untuk dinikmati oleh generasi akan datang. Dalam konteks global yang semakin terbuka, pelancong Islam yang berkunjung melalui MHPS dapat memainkan peranan penting dalam mempromosikan pemahaman antara budaya dan agama, mencipta perdamaian, dan menghapuskan stereotaip negatif. Oleh itu, adalah penting untuk mengambil langkah ini untuk menjana pertumbuhan pelancongan Islamik yang mampan di Sabah

Protracted development of stick tool use skills extends into adulthood in wild western chimpanzees

Tool use is considered a driving force behind the evolution of brain expansion and prolonged juvenile dependency in the hominin lineage. However, it remains rare across animals, possibly due to inherent constraints related to manual dexterity and cognitive abilities. In our study, we investigated the ontogeny of tool use in chimpanzees (Pan troglodytes), a species known for its extensive and flexible tool use behavior. We observed 70 wild chimpanzees across all ages and analyzed 1,460 stick use events filmed in the Taï National Park, Côte d’Ivoire during the chimpanzee attempts to retrieve high-nutrient, but difficult-to-access, foods. We found that chimpanzees increasingly utilized hand grips employing more than 1 independent digit as they matured. Such hand grips emerged at the age of 2, became predominant and fully functional at the age of 6, and ubiquitous at the age of 15, enhancing task accuracy. Adults adjusted their hand grip based on the specific task at hand, favoring power grips for pounding actions and intermediate grips that combine power and precision, for others. Highly protracted development of suitable actions to acquire hidden (i.e., larvae) compared to non-hidden (i.e., nut kernel) food was evident, with adult skill levels achieved only after 15 years, suggesting a pronounced cognitive learning component to task success. The prolonged time required for cognitive assimilation compared to neuromotor control points to selection pressure favoring the retention of learning capacities into adulthood

Antioxidant properties of MitoTEMPOL and its hydroxylamine

Piperidine nitroxides such as TEMPOL have been widely used as antioxidants in vitro and in vivo. MitoTEMPOL is a mitochondria-targeted derivative of TEMPOL designed to protect mitochondria from the oxidative damage that they accumulate, but once there is rapidly reduced to its hydroxylamine, MitoTEMPOL-H. As little is known about the antioxidant efficacy of hydroxylamines, this study has assessed the antioxidant activity of both MitoTEMPOL and MitoTEMPOL-H. The hydroxylamine was more effective at preventing lipid-peroxidation than MitoTEMPOL and decreased oxidative damage to mitochondrial DNA caused by menadione. In contrast to MitoTEMPOL, MitoTEMPOL-H has no superoxide dismutase activity and its antioxidant actions are likely to be mediated by hydrogen atom donation. Therefore, even though MitoTEMPOL is rapidly reduced to MitoTEMPOL-H in cells, it remains an effective antioxidant. Furthermore, as TEMPOL is also reduced to a hydroxylamine in vivo, many of its antioxidant effects may also be mediated by its hydroxylamine