Recent years have seen a surge in psychiatric diseases, which has resulted in considerable disease
distress and considerably decreased living conditions. Many considerable synthetic medications have
been used to treat these illnesses throughout the years, but they have been found to have limited
effects and substantial recurrence risks in many individuals. Mental illnesses such as depression
and anxiety are persistently on the rise around the world, posing serious challenges to the affected
person’s and their family members’ personal lives. There is mounting evidence that suggests the gut–
brain axis (GBA) contributes to the genesis and development of psychiatric diseases. This review
focuses on contemporary dietary therapies such as Mediterranean diets and dietary supplements
and emphasizes nutrition’s critical role in psychiatric care through the GBA. Several research have
indicated that dietary quality affects mental health because it controls metabolic processes, has
anti‑inflammatory and antiapoptotic characteristics, and promotes neurogenesis and synaptogenesis.
This study demonstrates many dietary components, their relationships to depression, and how they
work. The use of dietary recommendations to support mental health appears to be a novel, affordable,
useful, nonpharmacological intervention for people with mental problems.

Background: Tramadol has a high potential for misuse resulting in cognitive impairment.
Zingiber officinale, however, possesses neuroprotective qualities. Objective: Microscopically
assessed hippocampal CA1 and CA3 following Z. officinale and tramadol treatment.
Materials and Methods: Two milliliters/kilogram of distilled water was given to Group 1,
Groups 2–5 were administered 50 mg/kg of tramadol while Group 3 was also administered 12.5 mg/
kg of naltrexone, and Groups 4 and 5 were also administered 500, and 1000 mg/kg ethanol extract of
Z. officinale (EEZO), respectively, orally for 21 days. The rats were euthanized and their brains were
collected, fixed in 10% formal saline, and processed routinely using crystal fast violet (CFV) stain for
the demonstration of Nissl substance, glial fibrillary acidic protein (GFAP) for the demonstration of
astrocytes, and Hematoxylin and Eosin for general histoarchitecture and estimation of cell number and
volume using physical dissector and Cavalieri estimator, respectively. Results: CFV stain revealed
alterations in regions of CA1 and CA3 of the hippocampus presenting as indistinct staining intensity
and peripheral Nissl substance accumulation in the tramadol‑treated group. GFAP revealed numerous
reactive astrocyte processes. The area of reactive astrocytes remarkably increased (P < 0.05) and
the intensity of the Nissl substance remarkably reduced in the tramadol-exposed group. When
compared to the control, the tramadol-exposed group’s hippocampal volume considerably (P < 0.05)
decreased (coefficient of error [CE] =0.050). The tramadol treatment group (CE = 0.090) relative to
the control group (CE = 0.060) showed a striking decrease (P < 0.05) in the number of pyramidal
cells in the CA3 region. The tramadol treatment group (CE = 0.090) compared to the control
group (CE = 0.060) showed a striking decrease (P < 0.05) in the number of pyramidal cells in the
CA3 region. Tramadol toxicity was attenuated in the groups treated with EEZO in a dose-dependent
manner. Conclusion: Z. officinale possesses a potential neuroprotective effect against tramadol‑induced
neurotoxicity.

Tumor necrosis factor (TNF) plays a role in host cell defense. TNF‑alpha (TNF‑α), secreted from
macrophage has an important role in proinflammatory response mechanism. TNF‑α levels increase in
autoimmune, systemic inflammatory diseases, especially rheumatological diseases. Therefore, TNF‑α
inhibitors are alternant in the treatment of many inflammatory diseases. TNF‑α inhibitors are not
the first choice of clinicians due to their important adverse effects, despite the fact that successful
results in diseases treatments. Treatment with TNF‑α inhibitors causes different adverse effects
including many bacterial, viral and fungal infectious diseases, lung diseases, demyelinating diseases,
and malignancies. One of the most important adverse effect is tuberculosis (TB) by Mycobacterium
tuberculosis bacillus. TB occurs through reactivation in Latent TB infection. Thus, TB screening
tests appliedbefore TNF‑α inhibitors treatment have an importance. In this review, TNF‑α inhibitors
and their important adverse effect TB flaming were discussed, and also genetic background features
of these molecules have been explained.

In this review, the biological structure of garlic, its active ingredients, especially allicin and its way
of antimicrobial effects on cells evaluated and also the toxic possibility of allicin on diverse cells was
investigated. Various academic papers have been found in reliable literature. It is stated that garlic
includes lots of phytoconstituents with activities against cells. The toxic action of allicin on different
cell lines such as bacteria kinds such as Gram-positive (Staphylococcus aureus, Bacillus subtilis,
Streptococcus pneumoniae) and Gram-negative bacteria (Klebsiella pneumoniae, Helicobacter pylori,
Escherichia coli, Pseudomonas aeruginosa) for all that fungi like Candida albicans and parasites,
virus, glioma and human neuroblastoma cell lines and also oral tongue squamous cell carcinoma,
cancer cell lines which are characterized as malignant (leukemia, colon, gastric, and breast cell
lines) cancer. It has been revealed that, on those cells, allicin has also been demonstrated toxicity
mechanisms on cells like canceling deed of nitric oxide synthase, the peroxidation of lipids, nuclear
factor, kappa B, arranging cell period, modulating the activity of redox precision proteins and
influence cellular signaling.

The study of behavioral genetics holds great promise for revealing the genetic and environmental
factors that impact both typical and abnormal behavior. The ideas and techniques that have been
used to identifying the constituent parts of complex human characteristics serve as the foundation
for behavioral-genetic procedures. To analyze the genetic component of these complex features, new
tools are now accessible. We can start investigating how certain genes interact with environmental
variables in development as they are discovered. Important factors to take into account include how
we interpret these results, how we pose fresh questions, how we celebrate the information, and how
we make use of or abuse this knowledge. These problems are prevalent in all human research fields,
but they are particularly evident in human behavioral genetics. In this article, we review the results of
studies and theories, explore their implications for our knowledge of adult personality development,
and highlight outstanding issues that require more investigation.

Dear Editor,
Spinal cord injury (SCI) is a calamitous condition that
causes temporary or permanent changes in its function
resulting either from trauma or nontrauma.[1] The abrupt
nature of injury infers a radical change in various
domains on both persons with SCI (PwSCI) and their
family caregivers (FCGs).[2] The unanticipated nature of
this condition leaves the FCGs to adopt new roles and
responsibilities that they were not aware of it before.
The FCG’s psychosocial and vocational outcomes
are negatively impacted by taking on this additional
caregiver responsibility. This caregiving role puts them
in a phase where they often neglect their needs and
health.

Dear Editor,
A disease is considered rare disease (RD) when it affects
less than one in every 2000 people.[1] The World Health
Organization defines RD as a debilitating disease or lifelong
condition with a prevalence of one or less per 1000 people.
However, several developed and developing countries have
their own definitions. It is a health condition that affects a
smaller size of the individual patient population as compared
to other prevalent diseases in the general population and
has a startling social cost. The most common RDs include
autoimmune diseases and lysosomal storage disorders,
such as Pompe disease, Hirschsprung’s disease, Gaucher’s
disease, cystic fibrosis, hemangiomas, and specific types of
muscular dystrophies. The most common RDs that affect
children are hemophilia, thalassemia, sickle cell anemia,
and primary immunodeficiency.
RDs are often chronic, debilitating, and life‑threatening in
nature and can develop at any stage of life. Few of these
diseases are preventable and can lead to unfavorable living
conditions.[2,3] Less than five to seven individuals out of
10,000 are affected by RDs, although 6%–8% of the world’s
population is affected globally.[4] According to the Ministry
of Health and Family Welfare, 72–96 million Indians are
affected by RDs.[5] According to Orphanet data, among the
6172 unique RDs, 71.9% were genetic and 69.9% were
disproportionately impacting children.[6] The scientific
knowledge and medical understanding of RDs is inadequate
due to their complexity, heterogeneity, and ever‑evolving field.
RD awareness, as well as a lack of treatment alternatives,
may make the entire process from diagnosis to therapy
difficult and uncertain. RDs have emerged as a primary public
health priority owing to the challenges imposed by their low
prevalence, especially their continuous, life‑threatening nature
and lack of information and expertise.[7]
There is inadequate epidemiological data to quantify the
burden, and research and development options are limited.
It is difficult to estimate the exact number of people affected
by RDs, as the majority of RDs are not documented, except
in certain developed countries. Government indecision on
the provision of health‑care access is caused by gaps in
the maintenance of electronic health records or registers
of cases noticed in the underprivileged and vulnerable
sectors of society. Clinical trials are a crucial component
of the drug discovery process. It is completed in stages and
involves identifying numerous individuals suffering from
particular medical conditions and developing a robust trial
design to demonstrate the efficacy of the medicine. This
issue significantly worsened in the case of RDs. Finding
patients qualified for clinical trials typically involves
The Burden of Rarity: Rare Diseases and Future Perspectives
Editorial
significant search expenses. Given the rarity of patients and
in their entire professional careers, a significant percentage
of doctors in practice reported never having seen a
patient with a RD,[8] finding the correct diagnosis takes a
substantial amount of time. Clinical trials are expected to
be expensive because pharmaceutical companies will most
likely have to spend a substantial amount of money.
RDs affect not only the individuals who suffer from them but
also their families and communities. Due to the prohibitively
high cost of treatment, the impact on families is frequently
disastrous in terms of both the emotional and financial
tolls. Often, the patients’ and their caregivers’ medical
and social needs are unmet, which leads to experiencing
a severe psychosocial burden.[9] The individuals with RDs
and their family caregivers’ vocational aspects (education
and employment) will be adversely affected due to the
difficulty in accessing health‑care medical services for the
management of RDs, which leads to poor health outcomes.
A qualitative study from the USA reported that individuals
with RDs had experienced three types of stigma: Structurally
enacted, interpersonally enacted, and felt stigma.[10]
There is a need to enhance the awareness, advocacy, and
implementation of outreach programs about these RDs in
low‑income countries, among marginalized, poor literacy
populations. However, research on the impact of RDs on
psychosocial, economic, and vocational aspects of individuals
with RDs and their family caregivers globally is lacking.
Individuals with RD’s cannot afford health‑care services
due to the high cost of treatment, diagnostic evaluations,
medications, etc., especially in developing countries.
Usually, healthcare end‑up spending is spent on people
who are diagnosed late. This may often result in a terminal
patient who needs to be managed with expensive therapies
and rehabilitation. The government can implement the early
detection programs, as it can save time and resources and
reduce costs. A patient can be managed with less costly
interventions while providing better care and quality of
life. Early screening and diagnosis of RDs are critical for
the prevention of perinatal and neonatal disorders such as
Angelman syndrome, Carpenter syndrome, craniofacial
disorder, Hutchinson‑Gilford progeria syndrome, and
Wiedemann‑Rautenstrauch syndrome. In addition, drug
development can be performed using an artificial intelligence
algorithm that can potentially reduce costs and preclinical
work compared to a fraction of traditional methods. The
electronic health records of patients with RDs should be
should be introduced and maintained so as to aid in future
researches on RDs. From this data, crucial health information
related to RD patterns can be identified regionally. 2023One of the best methods for a proactive approach to therapy is networking and the exchange of experiences. Networking is one of the most valuable assets for people with RDs. Having a community will not only be a poignant reminder of the energy that people with RDs put into their lives every day but it will also be a valuable opportunity for them to feel less alienated in their ongoing struggles.In summary, the fact that effective therapies are frequently unavailable adds to the amount of agony and suffering experienced by patients and their families. The government must establish a plan to raise awareness of the severity and impact of RDs on patients and their families, and simultaneously conduct research and plan for better diagnosis and treatment, develop pharmaceuticals drugs that are accessible, affordable, and provide insurance coverage for treatment. Furthermore, patients with RDs typically face challenges owing to their low prevalence and lack of knowledge among their healthcare providers. As there is an urgent need to bridge the gap in physicians’ understanding of RDs, it is prudent to introduce additional courses on these diseases in the medical curriculum and postgraduate training for physicians. The internet is the primary source of information on RDs, and e‑learning programs and courses should be implemented for all medical practitioners.

Beyincik “küçük beyin” olarak bilinir. Beyincik, vücudun diğer kısımlarıyla olduğu gibi beynin de diğer kısımlarıyla bağlantıları nedeniyle motor koordinasyonu, denge ve kas elastikiyeti gibi fonksiyonların çalışmasını düzenler. Sıçan beyinciğinin fastigial çekirdek davranış üzerinde herhangi bir rol oynasın ya da oynamasın, referans belleği ve işleyen bellek şuanki çalışmanın konusunu oluşturmaktadır. Wistar albino sıçanının spino-serebellum’ unun bir parçası olarak fastigial nucleus, stereotaksik teknikler kullanılarak elektroliktik lezyon ile tek taraflı olarak(sol taraf) yok edilmiştir. Laboratuvar ortamında opere edilen hayvanlardaki gibi kontrollerle lezyondan sonra davranış, öğrenme ve hafıza 10. ve 15. günde artı labirent ve radyal labirent yükselten açık alan testi kullanılarak analiz edilmiştir. Davranıştaki değişimler 15. günde değil sadece 10. günde görülmüştür. Beyinciğinin hafıza sürecinde rol oynamadığı görülen gruplar arasında radyal labirentte hiçbir değişim görülmemiştir. 10. günde algılanan davranış değişiklikleri, iltihap azalacağı ve metabolizma normalleşeceği için 15. günde iyileşmesini takiben zarar gören kısımlardaki iltihap ya da zayıflamış metabolizma yüzünden olabilir. Bu sonuçlar göstermektedir ki fastigial çekirdek davranış ya da hafıza üzerinde herhangi bir rol oynamamaktadır.

Çeşitli çalışmalar, insanlarda bellek kontrolünün (anımsamada bastırma) yürütücü bir işlev olarak prefrontal korteks denetiminde aktif bir mekanizma ile gerçekleştiğini göstermiştir. Prefrontal korteksin ovaryen hormonların müdahalesine oldukça açık olduğu bilinmekle birlikte bu etkinin anımsamada bastırma işlevi sırasında nasıl bir rol oynadığı bilinmemektedir. Burada sunulan çalışma bir bellek kontrolü modeli olan düşün/düşünme paradigmasını (think /no think paradigm) kullanarak ve ovaryen hormonların kantitatif olarak analiz edildiği denek-içi desen düzeneği ile bu soruya cevap aramaktadır. Menstrual siklusun foliküler (düşük estrojen ve progesteron) ve midlüteal (yüksek estrojen ve progesteron) fazlarındaki bellek kontrol oranları kıyaslanmıştır. Veriler göstermektedir ki midlüteal fazda, deneklerin % 63.6 si, önceden öğrenilmiş kelime çiftlerini ‘düşünmeme koşulu’ yani ‘ip ucu kelimesi ile ilişkili hedef kelimesini düşünmeme koşulu’ (NT condition)- sırasında aktif unutma (anımsamada bastırma) becerisi göstermiştir (istatiksel olarak anlamlı bir şekilde kendiliğinden unutma oranına göre daha çok unutma ya da daha az hatırlama). Ancak ‘düşünmeme koşulunun’ bellek kontrolü üzerindeki bu etkisi, düşün/düşünme prosedürünü takiben yapılan bellek testleri ile gösterildiği gibi foliküler fazda gözlenmemiştir. Bu sonuçlar bellek kontrolü işleminin ovaryen hormonlar ile ilişkili bir durum olduğunu göstermektedir.

Agmantin, nöromodülatör ve nörotransmitter olarak çalışır. Davranışsal olarak agmatin, antidepresanvari etkiler uygular. Enzim olan agmatinaz, agmatini indirger ve böylece devre dışı bırakır. İnsan agmatinini kodlayan, bipolar bozukluk ve majör depresyonla bağlantılı olan bu genin konumu 1p36. kromozomdadır. Fakat bu enzim nöropsikiyatrik hastalıklar bağlamında henüz detaylı olarak incelenmemiştir. Duygusal bozuklukları olan bireylerin postmortem hipokampüsündeki agmatin protein dışavurumunu inceledik. Agmatin proteini, hipokampüs ve diğer beyin bölgelerindeki internöronlar altkümesinde saptanmıştır. Depresif hastalarda agmatin-immunopozitif hücre gövdelerinin sayısı ve sayısal çoğunluğu incelemedeki bütün kısımlarda (hipokampüs, habenula, insular korteks ve temporal korteks) fazlasıyla artmıştır. Agmatin doğal olarak arjininin kırılmasıyla/ bozulmasıyla ortaya çıkmaktadır. L-arjinin ve diğer katyonik amino asitlerin( L-lisin ve L-ornitin gibi) hücresel alınımına temel olarak katonyik amino asit transporter(CAT) proteinleri aracılık eder. Duygudurum bozukluğu olan hastalarda, hipokampüsün CA2 kısmındaki hCAT1 immunoreaktif nöronların sayısal yoğunluğunda sınırlı bir azalma vardı.